“Mailbag #8: What does the Fox say?” – with Dr. Nathan Fox

Welcome to today’s episode of “Healthful Woman,” a podcast designed to explore topics in women’s health at all stages of life. I am your host, Dr. Nathan Fox, an OBGYN and Maternal Fetal Medicine specialist practicing in New York City. At “Healthful Woman” I speak with leaders in the field to help you learn more about women’s health, pregnancy, and wellness.

All right, welcome to our eighth mailbag podcast, “What Does the Fox Say?” All right, let’s jump right into it. Great questions this week. First question from Caroline, “Hi, Dr. Fox. Your podcast is exceptional. I am a practicing midwife in Brooklyn working in a very busy and full-scope, arguably high-risk, private practice. I’m curious if you would consider doing an episode about the use of nitrous oxide in labor and delivery. I witnessed its use during a clinical rotation in the UK and we are currently piloting it at the hospital I deliver at. Thanks again.”

All right, great question. So, nitrous oxide is also known as laughing gas. It’s a type of anesthesia or analgesia or something that relieves pain that is inhaled, right, you breathe it in. It’s frequently used in dental procedures, for example. In terms of labor and delivery, it’s used a lot in England, in Scandinavian countries, Australia, New Zealand. It’s really not used that much in the U.S., not exactly sure why but it just happens to be that that’s the case. In terms of using it in labor and delivery, there’s a lot of benefits. First of all, it’s safe, right, the gas is safe for the mother and for the baby. It’s self-administered, meaning what happens is, like, if you go to the dentist frequently, they’ll put it on until you fall asleep, but the way it works in labor and delivery is the mother gets to hold the mask herself and put it up to her face when she wants to breathe in the nitrous oxide. And when she doesn’t, she takes the mask away from her face. And if she got so much that she would get boozy or pass out, then her hand and the mask would drop away from her face and it wears off within a minute. And so, basically, she would, you know, wake right back up. So, it’s not attached to someone’s face such that it’s always giving medication. It’s really up to the mother, she takes it when she wants it. So, that’s an advantage, that it’s safe. She can decide for herself when you want it, when you need it.

The difficult part of using it in labor is twofold. Number one, it takes about 30 to 60 seconds to fully kick in. And so, if you start taking it at the peak of a contraction, by the time it kicks in, the contraction’s probably already on its way down. So, there is some sort of finesse of timing to either do it the second the contraction starts or try to predict when the contraction is gonna start to take it. The other downside, it’s not a bad thing but downside, is it’s not as effective as something like an epidural. So, it’s a really a good option if someone wants some pain relief in labor but maybe not as much that will be provided by an epidural, or they want it but wanna have their mobility, which an epidural doesn’t really provide. So, it is definitely an option in labor and delivery. I think it’s something that will continue to grow in the U.S. for people who don’t want an epidural. There’s actually now a lot of people using it in the office setting. And spoiler alert, we’re actually starting to use it in our office. We just are piloting it right now for office procedures. So, that something that’s gonna be available in our office, and I think that’s definitely also a wave of the future. All right, great question.

Next question is from Grace. “Thank you for this podcast, it was very helpful. Is it possible to get a positive result for monosomy X from NIPT but end up being negative for an abnormality in both the placenta and the baby?” All right, so, a little bit of background. So NIPT, which stands for non-invasive prenatal testing, is, essentially, what we do nowadays, or what many people do nowadays, to screen for genetic abnormalities in the fetus during pregnancy. And, essentially, what it is it’s a blood test that’s taken from the mother, right, at around 9, 10, 11, 12 weeks of pregnancy. So, it’s drawn from her arm. And the blood goes to the lab. And what the lab can do is there’s always pieces of DNA that are in the mother’s blood, they’re floating around. And you can see these and you can separate them, you can find them. About 90-95% of that DNA is the mother’s DNA, which makes sense, it’s her blood, there may be, you know, DNA floating around. But about 5-10% is actually DNA that comes from the baby, or, more specifically, from the placenta. As the placenta breaks down, those cells release the DNA and it can go into the maternal circulation. And the lab is able to use the DNA from the baby versus the mother to screen for many genetic conditions or several genetic conditions in the fetus.

Now, the perfect screening test would be every time the blood test says “baby is normal, the baby’s normal” and every time the blood test says “the baby’s abnormal, the baby’s abnormal” that would be, like, 100% accurate. But that’s not how it is. It’s highly accurate, it’s very, very accurate, but it’s not 100%. And there is something called a false positive where you get a positive, which is, actually, abnormal, not like positive good but positive, like, as opposed to a negative test. And we try to confuse people in medicine, so, negative is good, positive is bad. So, you get a positive test that’s actually not true, that’s why it’s a screening test. And it’s definitely possible, right, to get a positive test on the NIPT and it not be true. There are ways to figure out what is the likelihood that this result is true versus not true, there’s tables and it’s based on exactly what is the abnormality, what is your age, all these factors go into it. But, basically, why would there be an abnormal test if there’s nothing wrong with the baby?

So, one reason is that, again, since the DNA comes from the placenta and not from the baby, there are times when there’s abnormal DNA in the placenta that’s not in the baby. Right? Typically, the DNA in the baby and the placenta are the same, and that’s what it’s like in most, if not almost all, pregnancies. But every now and again there’s abnormal DNA in the placenta, can be mosaicism or something abnormal in the placenta that’s not in the baby. So, could be that the test is 100% correct that there’s abnormal DNA in the mother’s blood but it’s not the DNA that’s actually in the baby. And so, that’s one reason you can do that.

Now, this particular question from Grace was saying, “Well, is there a way to have a false positive result where there’s abnormal DNA that’s not in the baby or in the placenta?” And the answer is yes, that can happen as well. Sometimes there is a pregnancy that looks like a singleton pregnancy but, in fact, there was a second twin that demised very early. So, maybe you don’t know it, maybe you didn’t see it on ultrasound, but there’s abnormal DNA floating around from that second twin that, again, not necessarily known by anybody but it could be there. There’s also rare instances where the abnormal DNA is actually the mother’s and not the baby’s, something that was unknown. Like, sometimes the mothers themselves have a very low line of what’s called mosaicism where most their DNA is normal and occasionally there’s a few that are abnormal. It’s rare but that can happen. And then there’s also chance these tests are not perfect and, so, there’s always a chance that someone’s…like, the amount of what they’re looking for is over the abnormal line but it’s just still normal. And that can happen in a lot of tests. So, the answer, Grace, is yes. You can absolutely have a positive result on the NIPT that does not reflect an abnormal baby and also does not reflect an abnormal placenta.

All right, next question is from Jennifer. “If the fallopian tubes were removed as a means of permanent sterilization, is there ever a chance they could regenerate?” Short answer, no. Long answer…okay, one of the options for contraception or birth control is having the fallopian tubes of the mother either tied or removed. This is something that we call permanent sterilization, permanent as opposed to temporary. So, temporary would be something like condoms, a pill, right, so they’re only effective while you’re using them and, when you stop, not effective. An IUD is long-acting, meaning it can be in for years but it’s still, technically, temporary because it can be removed but, if you do something like a surgical procedure, so, in a male a vasectomy, for example, is permanent and in a female removing the tubes or tying the tubes is called permanent.

Now, these types of sterilization can fail, they’re highly effective, as you would imagine, but they can fail. With tubes, most of the data on failure, meaning getting pregnant after having this done, is from people who had their tubes, what we call, tied, which is either they were, like, ligated with some sort of a clip that sort of squeezes the middle of them or sometimes a portion of the tube is removed, we call it a partial salpingectomy. There’s different ways to do that procedure. And yes, there is a failure rate for those procedures but it’s very low, it’s 1% or less, but it is possible to get pregnant after one of those procedures. If you have the tubes removed entirely, right, anatomically, it should never fail, right, someone should never get pregnant if the fallopian tube is absent because there’s really no way for the egg that’s leaving the ovary to get into the uterus because there’s no connection whatsoever. I suppose that there is, in theory, a possibility of failure but that’s probably if maybe the tube wasn’t actually completely removed or maybe the surgeon thought they removed the tube but maybe they removed something else. You know, these are, obviously, very, very unusual but I’m just thinking hypothetically how could it possibly fail. So, that’s sort of one thing. But the tubes don’t grow back. Right? If they’re removed, they’re going…it’s like, if you remove your appendix, right, if you have it taken out, you’re not gonna grow a new one. That’s not something that regenerates.

Why would someone have their tubes removed versus tied? There’s actually a lot of data on this. One of the reasons is, again, trying to make it more effective so you have a lower chance of failure. And there’s also recent data that removing the tubes entirely actually lowers the risk of certain cancers later in life, most notably ovarian cancer. And so, that’s something that’s discussed with people if they’re having tubes tied for sort of contraception reasons or if, let’s say, they’re doing a C-section and want their tubes tied, there’s usually discussion that says, “Well, would you like them tied versus removed? Here’s the risks, here’s the benefits.” And one of the benefits that comes up is it can lower your chance of getting cancer later in life, specifically ovarian cancer.

Okay, next question from Sarah. “Hi, Nate,” all right, this is a clue that this person knows me. “I know I could just text you,” there’s another clue, “but I think this is a basic question that could benefit others. Probably worth mentioning, I’m your niece, for the benefit of the listeners.” Hello, Sarah, my niece. Thank you for emailing in a question, thank you for telling me you emailed in a question. Hope you’re doing well, love to the family. All right, here is Sarah’s question, “What is the amount of time recommended to wait to conceive after having a C-section and why? Different doctors are saying different things, from 6 months to 2 years, so, I’m confused. Also, a little more broad here, but how does having a C-section affect a future pregnancy/birth? Feel free to use details of the circumstance of my C-section birth, if relevant. Thanks, and thank you for your amazing podcast.” All right, Sarah, thank you very much.

So, let’s start with the first part of the question, about how long should somebody wait after having a C-section to conceive. So, there is a reason that there’s a lot of confusion around this question. And it is true that there’s absolutely different things that people hear. One of the reasons is that the definition is confusing. So, for example, if you look at some research studies, how do they define the interval between one pregnancy and the next? So, one way to do it is if you take the date your first baby is born and the date your second baby is born, that’s the difference. So, if I have a baby born January 1st, 2024, and another baby January 1st, 2026, we call it a 2-year interval. So, that’s one way to define it. But another way to define it is from the date of delivery until the date you conceive. So, for example, if I have the same situation where January 1st, 2024, a baby’s born and January first, 2026, a baby is born, so, they’re 2 years apart, but the second pregnancy’s conception is gonna be sometime around, let’s say, March of 2025, I guess, so that’s 15 months. Or whatever it is, 13 months, 12 months. So, what do you call it, right?

And I think that’s part of the reason. Some studies look at the difference between births, some studies look at the difference between delivering and conception. And so, sometimes people are actually saying the same thing. So, for example, if one person hears, you know, “it should be six months” and another person hears “it should be 18 months,” they may actually be referring to the same thing. One person might be saying “6 months until you get pregnant” and the other person might be saying “18 months until you have the next baby.” And those are pretty similar, it’s probably 6 and 15 to 16 but you get the point, they’re pretty similar.

So, the first thing is to try to be very clear when we’re telling patients our recommendations and when we’re doing studies and when people are asking. What are we talking about? Right? Is it the time from delivery to conception or the time from delivery until the next delivery? So, that’s confusion number one and why some people hear different things or read different things.

The second reason there’s confusion is that the data about what is optimal is very limited. And the reason it’s limited is it’s very hard to sort of do a controlled study. Right? A controlled study would be I take, let’s say, you know, 1,000 women who just had a baby and I tell 500 of them, I have to randomly choose 500 and say, “You get pregnant in 4 months.” And I tell the next 500, “You wait 12 months and then get pregnant.” Right? That’s not gonna happen, it’s not practical. Even if you tell people something, that doesn’t really affect when they’re actually gonna get pregnant, right, because sometimes it takes longer, sometimes people get pregnant sooner. So, you can’t do a study like that.

So, what ends up happening is you sort of have to look backwards at who got pregnant early and who got pregnant later. And if you see a difference between, let’s say, the women who got pregnant early had some worse outcomes compared to the women who got pregnant later, you never really know is it because they got pregnant early, meaning something about the uterus not healing, the body not healing, not enough nutrients, you know, something like that, or is it just there’s something about women on average who get pregnant earlier that might be different from women who get pregnant later, for example, let’s say, access to medical care, access to birth control. Or maybe, you know, going back to work, not going back to work. You know, nursing, not nursing. Right? There’s all these variables that could affect, possibly, when someone gets pregnant that could also affect maybe the outcome. And so, if we see differences, we don’t know what we’re finding.

And there have been some actually pretty sophisticated studies that have looked at this. When you look at the less sophisticated studies, what seems to come out is that, if you get pregnant, and we haven’t even talked about C-section yet, just in general, if you get pregnant within six months of a birth, right, so, you have a birth and then you conceive less than six months later, it seems to be that there’s an increased risk of a lot of pregnancy complications, like preterm birth or the baby not growing well. And that’s sort of where this came from that said you should wait at least six months to conceive from one baby to conceiving the next.

However, those studies, again, as we were talking about, are somewhat flawed. The more sophisticated studies where they looked, let’s say, within a family said, “All right, we’re only gonna look at women who have three children and the interval between babies one and two was something and between two and three was something else. And when they did that,” right, because it’s the same woman, so, all the risk factors are the same, “they actually didn’t see a real difference between sort of a short inter-pregnancy interval and a longer one.” So, it’s possible that there’s actually no risk pregnancy-wise about getting pregnant early. The typical recommendation is to wait at least 6 months but the data supporting that, as I’ve gone over, is pretty weak or limited is what I would say.

Now, when you have a caesarean, there is an extra concern that’s on top of all the other concerns about getting pregnant early, and that is, “Will the scar in the uterus from the C-section have enough time to heal completely prior to the next pregnancy, specifically related to, if someone wants to labor and VBAC in the second pregnancy, will the scar have had enough time to heal in order to make it strong enough so that there is not a uterine rupture in the second pregnancy during labor?”

And so, there are data that the chance of a uterine rupture is higher in a second pregnancy and women who get pregnant less than six months after the first C-section. Which would sort of translate to, you know, whatever, 15 to 17 months between babies. And that’s sort of where I think people say, “At least 18 months.” So, the data suggests that, if you have a C-section, you should wait at least six months before conceiving or try to time your babies about 18 months apart, which is, you know, waiting 7, 8, 9 months, give or take, after having a baby. It’s hard to be more precise than that because, again, these studies are not perfect, they are limited. It’s not like if someone gets pregnant less than 6 months they’re gonna have a uterine rupture, it just, in those studies, the chance of uterine rupture instead of being 1% was, like, 2% or 2-3%. Again, hard to know how much of that is definitively because the scar didn’t have enough time to heal, although it’s plausible. Also, most people aren’t trying to get pregnant within the first six months of having a newborn, so, it doesn’t come up that often. But that’s the general advice, after a C-section, wait at least six months before trying to conceive. Whether it’s helpful to wait longer than 6 months, like waiting 12 months, which some people say, or 18 months some people say, it’s the data is not as clear on that in terms of risk of uterine rupture.

So, I tell people at least six months and, if they’re trying for a VBAC, maybe they wanna wait a little bit longer, like, you know, six months to a year or something like that. But it’s hard to be very precise other than saying, “Probably six months or more is the way to go.”

Sarah, in terms of the second part of your question, “How will it affect a future pregnancy or birth other than the issues surrounding VBAC?” Probably not much. There are some studies that suggest that some things might be slightly increased risk in a pregnancy after a C-section compared to after a vaginal delivery. But again, it’s not entirely clear if that’s due to the C-section specifically or risk factors for a C-section, which may also be risk factors for pregnancy outcome. So, if someone had a prior C-section, the main focus in terms of the next pregnancy and risk that’s different than if they had a vaginal birth is almost always or almost entirely surrounding the issue of labor, VBAC, uterine rupture, things like that. Again, it’s not a high risk but that’s the risk we’re talking about, and not so much in terms of the pregnancy itself. All right, Sarah, thank you for the question. Thanks for being a great niece.

All right, next question is from Penny, who is not a niece of mine. “Hi, Dr. Fox. Why are women required to drink twice as much glucose for the 3-hour glucose tolerance test as for the 1-hour screening test? Couldn’t scientists/labs develop adjusted target blood sugar levels for the 3-hour samples if you were only drinking 50 grams of glucose? Thanks from a patient who did two weeks of fingersticks because I couldn’t keep 100 grams of glucose down.” All right, Penny, great question.

In terms of screening for diabetes in pregnancy for gestational diabetes, part of the issue is we’re using studies that use certain screening tests. Right? So, if someone did do a large study and looked at a 3-hour test after 50 grams of glucose, maybe we would have that but I’m not familiar with that. Part of it is probably because 50 grams of glucose is a lot but not that much. And so, you may not get as much information about, you know, 2 or 3 hours after you take it as when you take more.

Now, it’s interesting that there are two main screening tests that are done for diabetes in pregnancy, one is the one you mentioned, which is a two-step process. Step number one is you take a 50-gram drink of glucose and then, 1 hour later, you get your blood drawn. And that’s sort of like you get a normal or abnormal and then, if you test normal, you’re done. If you test abnormal or a positive test, you go onto the next phase, which is a 100-gram test, like you’re talking about, but it’s actually for blood draws. You come in fasting, you have your blood drawn when you’re fasting, then you drink the 100 gram of glucose and then have your blood drawn 1 hours, 2 hours, 3 hours later. And then, typically, if two of those four values are abnormal, you get diagnosed with gestational diabetes. And if less than two, you don’t get diagnosed with it. That’s typically how it goes. There are some exceptions but that’s typical.

There’s another weight, which is actually 75 grams, so, in between 50 and 100, and that is 2 blood draws. You come in fasting and get your blood drawn, then you take 75 grams. And then, 2 hours later, you get your blood drawn. And then you have those two, and, again, there’s certain criteria for which of the two and how high they have to be to be considered having gestational diabetes. There is a lot of debate of which of those two screening paradigms is better. It seems to be that the first one is a little bit more annoying because it’s 2 steps and has 100 grams. But the second one is more likely to diagnose gestational diabetes, which may be a good thing, may be a bad thing, but it does not seem to improve outcomes overall. And so, people believe maybe it’s not a good thing to diagnose it in so many people.

All of this is difficult stuff because, again, the data is from studies that use absolute cut offs but sugar and sugar levels are not absolute cut offs. The higher it is, the worse it is, potentially. And so, it isn’t easy. I don’t think that they’re gonna be able to get a good enough test with just 50 grams, that’s my guess, 100 seems to work, 75 seems to be okay. So, if someone can’t tolerate 100, maybe they could tolerate 75. And like you said, for people who just can’t tolerate the drink, which absolutely happens from time to time, we’re sort of left with no great options. There are sort of certain options for taking things like jelly beans that have a fixed amount of glucose but it’s not as easy as you would think. Or to just do your fingersticks for a couple of weeks and see what they are, it’s not a perfect test either but it’s, basically, the best that we seem to have. Sorry you couldn’t keep the drink down, great question.

All right, the next question, two questions, is from Jordan. All right, “Jordan from Dallas here. I’m here from ‘The Toast,’ and I love the pod. I’m interested in hearing a discussion of blood work you recommend for women, even though it might not be routine. In February 21 I lost a pregnancy, likely because of hypothyroidism. Even though I see a primary care provider and OB regularly, no doctor ever checked my T4 and TSH,” those are thyroid tests, “until I miscarried. Lo behold, I have hypothyroidism that is now treated. Following that, I tried for two years to get pregnant and was unsuccessful until I learned from a hematologist that I was drastically iron-deficient. After two iron infusions, I was pregnant within two months. I now have a healthy 9-week-old.” Yay. “I always have wondered how my journey to motherhood would’ve been different if I’d had a clearer picture of my health and made adjustments accordingly. Thank you.”

Jordan, thank you for the question about hypothyroid and about anemia. I am very happy to hear about your healthy baby. So, it’s interesting because, as far as we know, having hypothyroid, unless it’s profound, right, it’s just a mild form of hypothyroid, actually does not seem to increase the risk of infertility or miscarriages. Now, obviously, I can’t speak to your specifics, your particulars, without knowing the numbers and your other health and this and that but, in general, it does not appear that people who have mild thyroid abnormalities have an increased risk of miscarriage. The data on that is pretty weak. The main reason that people debate whether to screen everybody in pregnancy for a thyroid issue, which is, again, like you said, checking a TSH, a thyroid stimulating hormone, or a TSH plus a T4, is actually related to a concern, a potential concern that having low thyroid, hypothyroid, could affect the neurodevelopment of the baby. That’s sort of where that came into play and that was the thought.

Now, severe thyroid abnormalities can do that but those are very rare. Mild thyroid abnormalities, like a mild hypothyroidism, which is what most people get diagnosed, have. It was thought that, by screening for it and treating that, you’re gonna lower the risk of neurodevelopmental problems in the babies. And so, that’s why it was done. But, actually, there have been very very large studies, well-designed studies where they randomized people to get their thyroid checked and, you know, fix, quote unquote, if there’s a mild abnormality versus not checking it at all. And they followed these babies out to, like, age five. You know, this was a big study and there was no difference. And so, the current recommendations are not to check thyroid routinely in pregnant women but only to check it in people who are higher-risk for thyroid abnormalities and, you know, other medical conditions potentially or have symptoms of thyroid abnormalities but not to do it routinely. So, that’s for thyroid.

And someone might say, “Well, what’s the big deal? Like, why not check it on everyone?” And that’s a fair question. It’s probably not a huge deal to check it on everyone but what ends up happening is there’s definitely a percentage of people who have a mild thyroid abnormality and even more who are sort of, quote unquote, borderline. And what ends up happening is, when people get blood tested routinely for thyroid and these results come up, someone sees it and usually what ends up happening is a lot more testing and treatments that may not be necessary. So, getting put on thyroid supplements, you know, thyroid medication, and getting more blood tests every month, every two months. Now, it’s not typically like a life-and-death thing but it could potentially cause side effects. It could be very annoying, give people a lot of anxiety that they now believe they have a condition or it’s gonna harm their baby when, if fact, the data doesn’t show that. So, that’s sort of the argument against testing everyone routinely and that’s sort of why the current recommendations are not to do it.

There’s certainly people who do, and, you know, I don’t begrudge them, that’s fine, but that’s sort of the main reason. So, it’s hard to say with your specifics without knowing all the results but, at least according to the best data we have, the miscarriage probably was not related to the thyroid and treating the thyroid is not known to lower the chance of miscarriage in the next pregnancy. There might be some other benefits, if you weren’t feeling well or whatnot. Okay, again, that’s just sort of as a general rule.

For anemia, pretty much everybody does screen for anemia and iron deficiency early in pregnancy. So, you know, part of the routine blood work that’s done and anybody in the beginning of pregnancy is checking a complete blood count, which includes sort of their hemoglobin, hematic rate, which is an assessment of how high your blood levels are. And if they are low, typically, the reason is iron deficiency. And that gets followed up, you know, check their iron and give iron. You know, there’s other reasons your blood count can be low that’s not iron deficiency, but that’s the most common. So, that typically is done. Again, also, interestingly, having iron deficiency and having anemia, unless it is profound and someone’s, like, ill, does not seem to impact the risk of fertility or miscarriage. There are issues maybe later in pregnancy, mostly related to the mother in terms of, you know, being weak or maybe after delivery, if you lose blood, needing a blood transfusion but it does not appear to affect the growth and development of the baby. Unless it’s really profound, like some people with sickle cell anemia who have, you know, really, really low blood counts sometimes, it can affect the growth of the baby, but not the kind that’s typically just picked up on someone without any symptoms.

So, again, it’s hard to know it without knowing your specifics but, as far as we know, at least from all the data we have, I don’t know if the iron deficiency was related to your miscarriage as well. And so, in terms of your overarching question, I don’t know if you would’ve had a healthy baby earlier had these things been screened earlier and treated earlier. Most of the data we have says that it would not have affected that but, again, we certainly don’t know everything. And it’s hard to know without knowing the specifics of your counts, but, in general, for the population that has been studied, and there are studies on them, it does not appear that it would’ve made a huge difference, as far as we can tell. But that’s very common in medicine that we don’t always know whether additional testing would’ve led to different outcomes or not. There’s a lot of uncertainty in general in medicine, and, obviously, there’s also situations where a study is reporting sort of the averages of a population but it may not be relevant to a specific individual, right, because all of us are different in many, many ways and it is possible that, in a given person, finding these and treating these could’ve helped them but it’s hard to know that for sure if we haven’t seen it sort of on large scales in studies with larger populations. All right, thank you all for these questions. Please, keep them coming, and we will keep doing the mailbag podcast. Hope you have a great day.

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