Thinking About Ob/Gyn
A fresh and evidence-based perspective of all things related to obstetrics and gynecology. Follow us on Instagram @thinkingaboutobgyn or visit thinkingaboutobgyn.com for show notes and more.
Thinking About Ob/Gyn
Episode 9.2 Circumvallate Placenta, Pregnancy Apps, Oral Meds for GDM, and HPV
In this episode, Howard and Antonia focuses on the evolving guidelines for HPV screening and the implications for women's health, highlighting its superior effectiveness over traditional Pap smear tests. Additionally, we explore the reliability of pregnancy apps for information and address a listener question about Group B Streptococcus screening and management.
• Discusses the transition to HPV testing as primary cervical cancer screening
• Reviews a recent study confirming HPV's effectiveness in preventing cervical cancer
• Examines the reliability and misinformation in pregnancy apps
• Answers listener questions regarding Group B Streptococcus management
00:00:01 Circumvallate Placenta
00:13:51 Evaluating Pregnancy Apps for Accuracy
00:26:56 Evaluating Risks of Pregnancy Apps
00:36:51 Gestational Diabetes Treatment Options
00:45:47 Manage GBS Risk Factors
Follow us on Instagram @thinkingaboutobgyn.
Welcome to Thinking About OB-GYN. Today's episode features Howard Harrell and Antonia Roberts.
Speaker 2:Howard.
Speaker 3:Antonia.
Speaker 2:What are we thinking about on today's episode?
Speaker 3:Well, we're going to review some new literature that's come out recently about real-life implementation of HPV screening as a primary means of screening for cervical cancer, and we're going to talk about some pregnancy apps and a new trial about medical management of gestational diabetes. And we have a great listener question about treatment of GBS unknown patients at term. But first, what's the thing we do without evidence?
Speaker 2:Okay, how about doing extra ultrasounds and antenatal testing for circumvallate placenta?
Speaker 3:Okay, yeah, that's a good one. So I think in the past, circumvallate placenta was thought to be associated with a lot of negative pregnancy outcomes, including abruption or maybe preterm birth or fetal growth restriction or even stillbirth, Because it would potentially be a type of chronic uterine synapses deficiency. If those outcomes are associated with it, then a lot of maternal fetal medicine docs and obstetricians have followed these patients when the diagnosis has been made with ultrasound, with something like serial growth ultrasounds and weekly or even twice weekly testing starting at 32 weeks, and overall treated this like it was a very important high-risk pregnancy condition.
Speaker 2:All right.
Speaker 2:So yeah, on ultrasound this might look like a peripheral rim of chorionic tissue around the placental edges that's echo-dense, and it's been described as the amniotic and chorionic membranes essentially doubling back or maybe tucking themselves in around that placental edge, and it's thought that the chorionic plate, or the side that faces the baby, in this condition ends up being smaller than the basal plate, which is the side of the placenta that faces the uterus, and this condition isn't always apparent until after delivery.
Speaker 2:But when people do see that echogenic rim at the edge of the placenta on ultrasound, then they'll just notate it as circumvallate. And then if you go ahead and Google that term, the AI bots that are probably populating the search results will tell you all kinds of crazy things. It causes everything from like fetal death or growth restriction or placental abruption and all kinds of really bad things. Results don't typically pull those things that it lists out from any kind of really high quality research studies, or maybe not even from research at all. It's just stuff that people throughout the recent past have speculated on that this could be a bad thing, and then they've written articles that show up in the Google search and then it makes the Googler think that it really is bad.
Speaker 3:Yeah, that's exactly right. The AI bots are good at averaging sort of the pulse of the internet and of course, over the last several years 20 years or plus that the internet's existed people have put on their webpages the think the Mayo webpages and all those that this is something to be concerned about, because we thought it might be. But it's not good at necessarily synthesizing latest literature. Maybe that'll change. There are some AI bots that specifically narrow their focus to peer-reviewed data and stuff. So that's an interesting way we're headed in the world, but right, so well then, people are driven by this concern to order tons of extra testing during the pregnancy, even for theoretical but yet unproven concerns, to ward off evil spirits. To be more safe than sorry, I suppose.
Speaker 3:But, like a lot of things, we started thinking that this was associated with all these negative outcomes, because when there's a negative outcome, we see a pregnancy with a negative outcome, and then we go back and look for causes and then you find out, hey, they had a circumvallate placenta. Maybe that's why they abrupted, maybe that's why they delivered early. And we make these associations without proving causality. So at some point someone who came in with premature rupture membranes or an abruption, or maybe even a neonatal or fetal demise. They might've had a placenta that looked circumvallate on gross examination or on pathology. And then we make that association between the two things and of course we want to find a cause. So we assume that there's a relation, because we have to blame the bad outcome on something. This is human nature.
Speaker 2:Yeah, don't you always say that association always means causation? Am I remembering that right?
Speaker 3:You might not be. You might not be.
Speaker 2:Okay, or the opposite, or no, no, it doesn't.
Speaker 3:Almost never.
Speaker 2:Right, right.
Speaker 3:But that's not the way our brains work, right.
Speaker 2:We're like.
Speaker 3:AI bots. We see two things and we link them.
Speaker 2:Yeah, and there's other examples of this too. It's the same thought process with a nuchal cord, for example, whether we see it at the time of delivery or especially when we see it on ultrasound. Then people get real scared of that, and that's likely come from the fact that if there's ever been a bad outcome and then they happen to have a nuchal cord, then people just assume those things are causally related and then those kinds of stories get spread around more anecdotally than anything else, or sometimes even in an uncontrolled case series.
Speaker 3:But the problem is there has to be adequate controls to understand whether or not these risks are really associated with the presence of this placental abnormality or a nuchal cord. In that case, when things go right, we don't often thoroughly inspect the placenta or send it to pathology or care about nuchal cords or circumvallate placentas or something like that. It's not usually our mindset to ask, hey, what caused things to go well and track the incidence of those things. So we're always searching for something when things go awry but this is the importance of controlled trials.
Speaker 2:Well, we're bringing up this particular thing because now there's some more recent evidence we can point to.
Speaker 2:So there was a study published in the May 2024 edition of the American Journal of Perinatology that finds that prenatal ultrasound findings of circumvallate placenta do not correlate with risks of adverse pregnancy outcomes.
Speaker 2:They conclude in that study that a prenatal diagnosis of this condition does not warrant additional surveillance during pregnancy, and they also review what was known previous to this study and they make it clear that the risks before they published this were previously unclear.
Speaker 2:We do know that certain other placental issues are specifically named in the ACOG committee opinion number 828 that's still current as of right now which lists reasons for increased fetal surveillance. So those things are chronic placental abruption, vasoprevia, filamentous insertion, then a two-vessel cord, which is more of a cord issue, and then under that same heading they also list oligohedramnios or poly, although I'd argue those are not really placental issues. But that's it. There's nothing else relating to the appearance of the placenta or the umbilical cord that is listed as a reason to do extra testing. But I know that many providers can have a bit of what we've called indication creep and they will just start kind of ordering these ultrasounds for other peripheral reasons, like circumvallate placenta is a common one, maybe some other thing that's been noted, like, let's say, bilobed placenta, placental lakes is a big one, or maybe just calcifications and any number of other things that are typically listed as descriptions of the placenta but do not have any established associations with perinatal outcomes.
Speaker 3:Yeah, and it's interesting in that paper that they said we really didn't know. It was an open matter that wasn't settled by science because, as you said, if you search for this online for five seconds you're going to be scared to death. And the truth is, prior to this paper it hadn't been studied in a way sufficient to really answer the question. But now we have this evidence. The ACOG practice bulletin list that you just reviewed recommends testing for chronic placental abruption once or twice weekly at the time of diagnosis, and for velomentous cord insertion and, as you said, single umbilical artery, starting at 36 weeks, not 32, and only once a week, and then for vasoprevia, it says to individualize your plan for the patient.
Speaker 2:Yeah.
Speaker 2:So I'm sure if there's any setting, any practice setting that does not have strict oversight by, let's say, an MFM or a department head who's committed to following guidelines for intranatal testing, then those recommendations that are listed, even for the conditions that are listed in there, are still going to be exceeded in some way.
Speaker 2:I've definitely seen people getting twice weekly testing for the two-vessel cord issue despite having normal fetal growth and, of course, any placental condition that is not on that list, people often will still use it as a reason for testing. Really, the placental lakes I've seen a ton Circumvaluate placenta. I think is just a bit more rare. But I can imagine the same people that order testing for placental lakes would probably order testing for that and by default. In that case they're just making up their own rules and their own testing schedule with no evidence to back it up. And if they're that concerned that they're going to go ahead and exceed the rules that have been recommended by ACOG, then they're probably going to pursue the maximal amount of testing that any patient is feasibly able to do, even if there's no testing indicated whatsoever feasibly able to do even if there's no testing indicated whatsoever.
Speaker 3:Yeah, we definitely do way too much unindicated antenatal testing in OB. That bulletin just rarely recommends twice weekly testing and that's usually associated with something really high risk like a preeclampsia diagnosis or growth restriction with absent end diastolic flow or very poorly controlled pre-gestational diabetes. But in many cases it says once or twice weekly. It gives you the choice and the wording I'm sure was fought over in those rooms and those committees went there and a four or three vote here and there over let's give the option for twice weekly, even though the science doesn't support or barely supports once weekly. That means, when they say it that way, that there's no evidence that twice weekly testing is superior than once weekly testing. It leaves some room for regional variation and pragmatic considerations and things like that. But the problem is it's more lucrative to do it twice a week than once a week.
Speaker 2:And that twice weekly testing really is not always feasible for patients. They have to often take time off work, arrange babysitting or those kinds of things and those tests can. It might just be a 20-minute NST or a 30-minute BPP, but the whole process takes a half day getting there, checking in, waiting, et cetera. A half day getting there, checking in, waiting, et cetera. And it just seems like once there's any finding whatsoever in the course of their prenatal care that is not completely routine and low risk and all within reference ranges, then it gets automatically treated as super high risk. And then you get stuck in this antenatal testing scheme.
Speaker 3:Yeah, and the thing is the bulletin is already very conservative, recommending testing that we know we've talked about on here is known to not improve outcomes, such as skull stasis or pregnancy or obesity, so we don't need to go beyond the already ultra conservative bulletin in arranging antenatal testing for things that they just don't have an indication.
Speaker 2:Agreed, all right. Well, let's shift to our next topic. We talked very recently about the transition to HPV-only testing as the primary mechanism of cervical cancer screening, and we talked about the possibility that this would increase detection rates and further drive down cervical cancer deaths, mainly by getting to those vulnerable patients who, for this kind of test, could be able to just give a urine specimen or a self-collected vaginal swab but would not be as able to come in for a full-on speculum exam and PAP, and by not having to go in for a pelvic exam. Many of those more vulnerable populations now have more access to screening than they did before, but for the most part, that idea that by reaching more people we decrease cancer deaths has still been theoretic.
Speaker 3:Right, and it's not like cervical cytology would never happen. We would need to collect cytology if the HPV result came back positive. So it's just a question of do we reflex from cytology to HPV, like we've been doing predominantly, especially in women under 30, or do we reflex from HPV to cytology? So if we're starting with HPV rather than cytology, it gives us the opportunity to expand how many patients we collect, because you can self-collect. Maybe very soon we'll be doing it by urine, for example.
Speaker 2:Right and because, right now at least, it's just not feasible to self-collect cytology and get a quality, reliable specimen. So there's a new trial published in the Lancet in November 2024, that looks at this question of does increased access with HPV actually help improve detection? There was a group in Sweden who studied the real-life results of changing these guidelines to start with HPV rather than cytology and they looked at the impact of rates of cervical cancer in Sweden. And yeah, they just essentially changed from a cytology first to an HPV first approach and then they tracked the outcomes?
Speaker 3:Yeah, and they found that the HPV-based screening was significantly better at preventing invasive cervical cancer. In this real-world setting. In this real world setting, in fact, the women who are HPV negative had only a 1.3 per 100,000 person years risk of cervical cancer 1.3, but women who had a negative pap smear, in other words, normal cytology, had a 9.1 per 100,000 person year risk, and women with normal cells but who were HPV positive so that would be our patients after 30, for example. But normal cytology who are HPV positive had a 79.2 per 100,000 person-year risk, and if that was either HPV 16 or 18, with a normal pap smear, they had a 318.2 per 100,000 person-year risk. Remember, that compares to a 1.3 per 100,000 person-year risk with just HPV negative.
Speaker 2:Yeah. So those numbers show pretty clearly that having negative HPV test is much more reassuring than having negative cytology on a pap smear. But, more importantly, there's a population of women with normal pap smears who have not been getting HPV testing because there was no indication for reflex, maybe due to their age group, for example, or maybe because they were in the right age group, but, like we said that, their providers don't do co-testing.
Speaker 3:Or they were doing the Q3 cytology rather than because it's still been in the guidelines.
Speaker 2:Yeah, and so those women could be like normal cells but then unknowingly have HPV 16 or 18, and they would be at nearly 300 times the risk of cervical cancer per year compared to someone who had had the HPV screening. That was negative, so the conventional screening guidelines are just completely missing those women.
Speaker 3:So this improves that and then, as we said, it hopefully improves the number of women who are going to get screened, by making it easier to either self-collect or urine collect these, and as we go on, I think we'll see more and more evidence about this.
Speaker 2:Yeah. So maybe a potential counter argument, at least in the U, would be isn't it even better for women 30 and up to get both co testing HPV and cytology up front every five years? If they're normal, then only getting HPV? My residency program, while I was training there, actually brought in a guest lecturer during one of our academic sessions to make this exact argument that HPV only screening would miss patients that co-testing could catch. Now this has been several years ago, way before these self-collection kits were approved, but I'm assuming they're referring to those rare cases of you might see someone with abnormal cells but HPV negative. So the counter argument might be what's wrong with continuing what we're already doing for women in that age group?
Speaker 3:Well, I've seen that talk a couple of times as well, and I will point out that those talks are usually funded by ThinPep and SurePath because they're facing a existential crisis, potentially on losing a whole business industry as this gets replaced. But I think the main thing that's wrong with it is the cytology false positives and the impediments that requiring a pelvic exam creates for the population's most at risk, and this is why real-world implementation studies are important. What folks should take away from this study is that if a pap smear, even with modern liquid-based cytology, it's just not that good, it's not anywhere as good as people thought it was. It's way better than conventional pap smears were, but it's not good compared to HPV screening, and what you should want is HPV screening.
Speaker 3:Cytology doesn't really add anything to the elimination of cervical cancer or precancerous morbidity, and it might stand in the way of a large portion of the population from seeking care or getting them, since it can't be self-collected and involves this invasive, uncomfortable procedure that women don't want. They did find in this study that more women were likely to get screened in the presence of the only requirement being HPV, and they showed that they cut down on the number of cervical cancer diagnoses in their population after eight years of enrollment. So this isn't theoretic, it works and it's how we can continue to reduce cervical cancer morbidity and mortality in the United States and enhance screening and screen the most vulnerable populations, where cervical cancer is most impactful of patients who just aren't getting screened because of the nature of how we're doing the screening.
Speaker 2:I've been telling my patients lately to stay tuned for these changes. We don't have this screening system just yet, but I'm hoping they'll have it very soon, and since I've been bringing it up, I've never met anyone who reacted somehow with sadness at the idea that they wouldn't need to keep getting routine speculum exams for their paps. Okay, we'll move on to the next topic then. So there was a study in November 2024 that was a systematic review of pregnancy apps for smartphones. Review of pregnancy apps for smartphones. They wanted to look at what features these apps have and also how scientific the information might be that's in the apps and how they were being commercialized, along with the user's experiences.
Speaker 3:Yeah, and this isn't the first study certainly to look at this. These are fairly easy studies for fellows and residents to do, I think, but they tried to be more comprehensive than some of the prior studies. They did a good literature review of that prior literature and noted some areas where information was inaccurate or inadequate, particularly on these apps concerning things like nutrition information and weight gain during pregnancy, or the meaning and implementation of kick count routines, or even topics like exercise and alcohol intake. They found a lot of information that was just inconsistent or incorrect and they also noted similar misinformation issues around things like immunizations, hair dye safety, breastfeeding misinformation, things like that. So there's that aspect of how accurate is this information. But even when information was cited, there usually weren't references and they have this sense that users still have a preference and they have some literature for this for information provided by their physicians or by relevant medical organizations or by the scientific consensus rather than just people's opinions.
Speaker 2:That's an interesting find, I think, because often we're overwhelmed by what's really just a minority of patients that come in with very strong beliefs in false information and a very strong distrust and kind of an antagonism towards the medical establishment and kind of an antagonism towards the medical establishment, and then just dealing with that minority can make us feel like we're always defending our evidence-based guidelines and that it's just a losing battle because there's some people that just will refuse to accept certain evidence-based facts. We've talked before about things like I'd still say fringe, anti-vaccine and anti-hospital community births out there as just two easy examples, and we have to remember, then, that that's a minority. The majority of our pregnant patients do trust us. They come to us and they want the information we have to give them. They trust our medical societies. They don't think it's just all a big conspiracy. They want high quality information from people that have been educated and are professionals in that field, and these pregnancy apps are often not delivering it. So that's the theme of this published review.
Speaker 2:These apps are built out perhaps by people who are not content experts, and they include features that might be more likely to gain popularity and more users and, of course, to make more money, but those things may be at the cost of accuracy. I remember I used a popular free app I don't think I need to name it, but it was during my pregnancies and it just had the opening screen Every week, would show me how big the baby was compared to some fun object, like fruit or a toy or like a cute baby animal or something, and it would have a little picture and then some animations of a fetus at that age. And even for me it was just a fun thing to look at, even though I knew some of the information I had to take with a grain of salt. But most patients are not board-certified OBGYNs like I am, and they'll look at this same app and they won't know which areas of the content are actually iffy, yeah same app and they won't know which areas of the content are actually iffy.
Speaker 3:Yeah, and the popularity of apps aren't necessarily consistent with accuracy of information, because they may be popular due to some of these clever designs or things that drive engagement.
Speaker 3:There was another area in this study that I thought was interesting. They talk about how these apps that they may have disease screening functions and overall that might cause harm, both in leading to higher rates of depression and anxiety, and something they call cyberchondria, where folks essentially convince themselves that they have certain diseases or problems without really understanding, of course, how the diagnosis is made or how common the disease is, or understanding whether they even really have it, and then they go down rabbit holes of anxiety-laden internet searches and get worked up about a disease that they perhaps don't even have. Doctors do this too, when they spend too much time giving patients a laundry list of symptoms to worry about, and then, of course, the patient becomes anxious about those symptoms. A segment of patients do, and it's more likely for them to experience those symptoms because they've been warned about them, and the apps do this and then believe that they have them, and they point out that there's evidence that this just increases this what they call again cyberchondria, but this medical anxiety.
Speaker 2:Yeah, that's an interesting term. I'll have to remember that. And in the study they also talk here about how some of these apps are really designed to promote more engagement, so more use of the app, and that just can contribute to more smartphone addiction, which is already more prevalent in female users. And the thing about disease screening features in these apps is interesting. And the thing about disease screening features in these apps is interesting. I think it's like it's trying to provide a telehealth type service. I'm thinking again of our prior discussion of prenatal care and how people could theoretically take their blood pressures at home and then barely ever need to come in for an actual office visit. But when these apps try to do that kind of a thing, coupled with inaccurate information, it's not actually providing any kind of service, at least not in a helpful way.
Speaker 3:Right and they'll pair more and more with health data from wearables and non-invasive monitors think Apple watches and things like that and build out this information that we don't recommend screening for and we don't necessarily know how to interpret.
Speaker 3:That may further anxiety too. We should talk sometime more at length about blood pressure cuffs and how accurate these blood pressure measurements are with these home ambulatory cuffs. But just as a reminder, studies have found that extra home blood pressure cuffs they're not very accurate and that even with validated home blood pressure cuffs in a clinical study, when you take these extra measurements at home in between visits, they've not been shown to improve pregnancy outcomes. So we don't recommend that patients check their blood pressure at home in between their regular visits, and maybe we can come back to that when we have time to do it in a future episode. But a health screener in one of these apps might ask a patient questions about, say, do you have headache, do you have swelling, are you seeing spots? And then ask them to check their blood pressure with a cuff. That's very inaccurate. So she does, and then she comes to the emergency department at 20 weeks because she's convinced she has preeclampsia with severe features.
Speaker 2:Yeah, and there is a role in medicine, of course, including in obstetrics, for home blood pressure monitoring, but it has to be done right, and so often I see people reporting that they had high blood pressures at home when they come into the office or hospital. They're all completely normal, not even a single mild pressure. So I think that the apps and the home blood pressure cuffs may be driving some of this. There are definite pitfalls with the counseling in these apps, as well as the disease screeners and those screeners diagnostic criteria. They, for example, they really should never be asking about edema as an assessment for preeclampsia, because that has not been part of the criteria for 30 years or more and most pregnant women are going to see some spots at various times during their pregnancy. But that's not the same as scotomata. That's more specific to preeclampsia. So patients might have, they might sit up too fast or rub their eyes and have innocuous floaters and then their hands are a little swollen and they'll scroll through one of these apps and think they're about to die of preeclampsia.
Speaker 3:The apps also tend to amalgamate, much like AI does, what you might call conventional wisdom or crowdsourced wisdom from the internet. I mean, maybe AI writes some of the content frankly, without any expert editorial oversight. So dietary and exercise advice is often very dated and overly restrictive or constrictive, and things like the description of preeclampsia, as you just mentioned, might be outdated and overly broad and include symptoms that we don't really think have specificity for preeclampsia anymore. And they're not doing much work to get only fact-based and evidence-based data on these apps. They're usually compiled by non-physicians who go through and do Google searches and rewrite whatever the internet has to say and create an app that serves as a funnel for some product they're selling.
Speaker 2:Well for a fair price. I'd love to help one of these app companies put out actually correct information, but it takes work and it takes very frequent updating and I'm guessing the app developers don't want to put in the extra resources for that. If they're already getting the users that they're looking for, why make it harder on themselves they're looking for? Why make it harder on themselves? And especially now they can just use a chat GPT little widget to create a lot of the app and that saves them more time. But of course it includes a lot of content that's not validated. They listed the most common features of all of the apps and that included the week-by-week pregnancy progress information like how I mentioned, that would say, the typical size and what organs have developed and such, and who doesn't love that? And then they also include sections with general medical information and that's where there can be a lot of inaccurate recommendations. And then another common function they found was some kind of physiologic data tracker.
Speaker 3:And these sorts of things are very popular, if you think about the Apple Health app or something like that for Android, where people are invited to put in all sorts of daily or weekly information tracking their pregnancy. So the apps might ask you things like to put in your weight or what you've eaten today, or what activities you've been doing, how's your skin, how's your mood, how is your sleep, and then, of course, check your blood pressure. But again, we don't recommend that kind of hypervigilant tracking of all those things for pregnant women and we don't recommend that pregnant women universally check their blood pressures at home. So none of those particular items need to be tracked more commonly than at your regular prenatal visits. And then they create an opportunity for anxiety, overdiagnosis, smartphone addiction, et cetera, without improving pregnancy outcomes.
Speaker 2:Yeah, I remember previously in my pregnancies that was when I was first getting these smart watches I assumed this already existed, but I looked long and hard for an app that would just.
Speaker 2:Previously in my pregnancies that was when I was first getting these smartwatches I assumed this already existed, but I looked long and hard for an app that would just effortlessly integrate information and then give me like some kind of calculated recommendation. I wanted something what fitness trackers already exist, but then with some kind of overlay, that's a pregnancy setting or a postpartum or a breastfeeding setting. But all of the apps I found were just like little journals, like they would just collect the clicks and then that's it, and it just was not going to be super useful just to scroll back later and look at oh, this night I slept six hours, this night was seven. Now you need to sleep more, or now you need to walk more or now you need to drink more water. But they really can't do that because likely because it's way too complicated to actually physiologically customize anything to a particular person, especially during pregnancy, and also because none of that has been proven to help at all.
Speaker 3:And, frankly, I think if you're relying on your smartphone to tell you if you're too tired or thirsty, you might be relying on it too much. If you're tired, sleep more. If you're thirsty, drink water.
Speaker 2:Yeah, and that's honestly what I would tell a patient too, I think. Now I've had the smartwatches for a while longer and the initial novelty of it has worn off and I don't, thankfully, pay as much attention to it. But I guess that's how they get you. I think the last smartwatch I got had added like a temperature tracker that was supposed to help like with fertility stuff, and I thought that was interesting, but I have not used that one bit. So anyway, back to this paper. There was a pretty long list of other functions in these pregnancy apps. There was over 30 functions, but a lot of them then included ways of monetizing the app, so they might have a shopping list function or a list of birth classes or whatever kind of community tie-ins to sponsors of the app.
Speaker 3:Basically, Right 20 years ago or so. I remember investigating cord blood banking companies and I actually pulled the SEC filings of one of the leading companies at the time. I'm real fun at parties and I looked at their advertising budget and how they spent their money, and the majority of their budget at the time was spent on a dozen or so different websites this is in the early 2000s that provided pregnancy information or pregnancy message boards. I think almost all of them had a community message board type feature and when I went and looked at them it wasn't obvious that any of these websites were owned by the company that was selling the product. But when you went into the information sections, or if you went into a discussion board or something like that, all of a sudden here's somebody recommending and talking about core blood banking and oh, have you heard about this company and that sort of thing?
Speaker 3:And people would make these occasional posts and there was no indication that they perhaps worked for the company, but they would start these discussions.
Speaker 3:You'd even see the same people on different boards, right, because they're clearly an employee of the company, and they would talk about the research that had been done and what their doctor might have told them or how important it was to do blood banking on a post that's women talking about back pain or something, and it was all obviously things slid in there by the company. So we live in an age where the product is being advertised in a sneaky and covert way these apps. You don't necessarily know what you're being sold, they may not even know If they can build an audience. They'll find someone who's interested in the data that's being collected in that audience and then the app serves as a funnel to get you to some other point where you'll be sold a service or a product like a vitamin or a supplement or an online doula or online counseling or some pregnancy support, whatever. But they did find that basically every one of these apps had some commercial application to make money off the user, that they were all meant to be funnels.
Speaker 2:That's really just the whole internet today. Whenever you watch a video or reel on any social media platform, it's not obvious to the viewer that the creator is likely part of some effort to promote a product or, conversely, to dissuade viewers from using like a competitor type product because it's in the best interest of another company. But a lot of what might look organic homemade is actually funded and produced by commercial agencies that are professionals in trying to get views and clicks and to sell stuff because they're being paid to do it, and so a pregnancy app is a really easy thing to develop and serve as a funnel to sell some other product, and even if only 1% of users were to click something, then that's going to more than justify the cost of the app development and distribution. So it's not about helping pregnant women, it's not about teaching them correct information, it's about getting the clicks.
Speaker 3:Well, I think the summary of all this is we, as physicians or midwives, need to know more about these apps, and that some of them might be doing more harm than good. We probably need to actually just give recommendations on apps that we've looked at and feel like are higher quality or have better information, in order to protect our patients from just being abused by them.
Speaker 2:Yeah, and we need to be providing most of the education to our patients, but most of what they're hearing, rather than us being just 1% of what they're learning and everything else is from the internet. The most of the patients actually want that and they trust us above other sources most of the time, and so you and I have used the website wonderfulpregnancycom a good plug here. So you created this website as a way to have some vetted information for patients. There are no affiliate links. There's no sponsors. This is essentially just a public service out of your own pocket, and anything you might recoup back would be from people buying the book version of this website, not from clicking a link, not from any advertisers and that book now is available to purchase, so we'll put a link to that too.
Speaker 3:Now we sound like a funnel.
Speaker 2:Well, we do. I know it's sometimes hard to tell one from another.
Speaker 3:We make no money off of it, but it is nice to be able to tell patients, hey, just go to this website and if you have questions that are on there, let us know, and that's why we. That's why we've done that. I'll add quickly that sometimes the motivation isn't financial. For some folks it may be agenda driven. So if you're promoting an agenda, say being against vaccines, then you'll want to produce content that funnels people in that direction. So 95% of your content may be great, but then you pepper in your agenda or whatever it is, and so our agenda with this podcast or with Wonderful Pregnancy website or things like that, are just to try to promote accurate and practical information that empowers our patients and the people who take care of them.
Speaker 3:So another feature of the apps that I'll mention just quickly are birth plan creation features, and they contain a lot of bad options. We did an episode once on birth plans. We looked at the bumpcom and some of these birth plans and they contain just a lot of options that patients that are not options are not good options, and so that's another area where you're better off just offering patients a vetted source of options to help them make a birth plan if they want. We do that on Wonderful Pregnancy or in the book version of Wonderful Pregnancy, just so we've given choices that are evidence-based and good choices and the patient can look at those but not tell them. Just crazy things on there too, like lotus birth.
Speaker 2:All right, well, let's move on. There's a trial published in January 6th of 2025 in JAMA. That was a randomized controlled trial of oral glucose-lowering agents versus insulin for gestational diabetes. So for a number of years we've entertained the idea of using orals like metformin, and previously glyburide, for treating gestational diabetes. But after some time we saw there really wasn't compelling data that this was any better than insulin, and insulin already was the gold standard. And we know that there might be some still unknown harms of metformin and glyburide because they both cross the placenta and we don't have those long-term studies of do they get cancer as adults or something. We don't have that yet. That could still be something there. Whereas with insulin it does not cross the placenta, we know it has a great safety profile In the UK and other European areas. Metformin has continued actually to be a gold standard for treatment of gestational diabetes. So these authors of this paper conducted a randomized controlled trial that was a non-inferiority study to try to compare orals versus insulin Right.
Speaker 3:So they randomized 820 participants at 25 different Dutch birthing centers who had gestational diabetes that wasn't sufficiently controlled after two weeks of suggested dietary changes. So they either received metformin that was titrated up from initial 500 milligrams a day to as much as they were tolerate, with the goal of being 2000 a day in divided doses, or insulin, and they would add gliburide to the metformin group if the metformin at maximum tolerable dose was inadequate. And, of course, eventually they'd add insulin to those patients if both of the oral agents were inadequate. Now, the primary outcome they looked at was the percentage of infants who were large for gestational age at birth, but they also included all the secondary outcomes that you would imagine, things like rates of hypertension, incisoring delivery and NICU admission rates and birth injuries due to shoulder dystocia or otherwise and things like that.
Speaker 2:Yeah. So they found 23.9% of the infants in the oral group were large for gestational age at birth, compared to 19.9% in the insulin group, and so this failed their standard for non-inferiority. None of the other secondary outcomes were any different, but interestingly, maternal hypoglycemia was reported in 20.9% of patients on orals compared to 10.9% of patients on insulin, and I think that's interesting. At first blush it might strike people as being counterintuitive. People might think initially that hypoglycemia is more likely on insulin. But you are our resident diabetic for this podcast, so what do you think about that?
Speaker 3:Yeah, I think people are scared of insulin for no good reason and there's always just been a bias against it.
Speaker 3:If you can keep somebody on orals rather than have them take a shot, that feels like a good thing.
Speaker 3:So my whole life I've seen doctors again doing everything with think type 2 diabetics to avoid the shot, and then of course they project this fear of injectables onto the patient. But the typical insulin that we would use in almost all gestational diabetes cases is a long-acting insulin like Lantus or one of its biosimilars, and at a relatively low dose, and those medicines just don't really have the ability to make a person become hypoglycemic and they really have no significant side effects other than burning at injection site. I guess it is more acidic, so it does burn a little bit, but Gleburide definitely can make you hypoglycemic. And metformin well, it won't make you hypoglycemic, but it has significant GI side effects, and so a well-informed patient actually would probably rather choose insulin once a day, with no real systemic side effects and a lower likelihood of making her hypoglycemic, as opposed to taking some sometimes multiple pills a day, four big metformin pills a day, maybe three gliburide pills a day and then having diarrhea and having episodes of low blood sugars after dinner, if she didn't need enough.
Speaker 2:All right, then I'll also point out the four percentage point reduction in macrosomia didn't result in a statistically significant reduction in other outcomes that they looked at, but there were four birth injuries in the orals group compared to zero in the insulin group. So that at least suggests that maybe the study was just underpowered to call that statistically different, but it was close. Perhaps a larger study that was actually powered towards birth injury rates in particular may have shown a difference. And the fetal weights in the insulin group are a little bit less on average and you just never know where maybe a couple hundred grams of body weight could be the difference between birth injury versus an uncomplicated birth.
Speaker 3:Yeah, At the margin that may be the difference, so, but underpowered to answer that definitively. So we'll see if this changes European practice, but certainly in the US, of course, we'll continue to recommend insulin as a preferred therapy for gestational diabetes. I do have to say I see a lot of patients who are still given metformin or gluburide rather than insulin in the US.
Speaker 2:I haven't seen as much gliburide, but I do see a whole lot of metformin and I will prescribe it too. Maybe I need to reevaluate my counseling. But I feel like I frequently encounter patients that want to avoid needles at all costs. And we're just doing that because maybe as a holdover. And but we're just doing that because maybe as a holdover, maybe it's like a take a week or two to get used to this idea and then eventually we'll add the insulin on. But a lot of patients, I think, are just refusing insulin at first.
Speaker 3:Yes, definitely the idea of a needle is scary, or even just the implications of I'm on insulin and so we've done that to them. Maybe I think it's again how we counsel patients I'm on insulin and so we've done that to them. Maybe I think it's again how we counsel patients. So I don't that often have patients refusing insulin, but then I see other patients from other physicians and basically all their patients refuse insulin. So I think that there is devil in the details about how we counsel them, which is my point about understanding the hypoglycemia risks and the side effect risks. If you're putting that stuff in there, then you may make a difference. And then certainly, if you're telling them that we believe that the insulin is proven superior and has a smaller birth weight associated with it which is one of the goals and, again, less hypoglycemia and less GI side effects and all that, that might change the adoption rate of insulin for patients who have some hesitation.
Speaker 2:Okay, well, we do have a great listener question. We talked very recently about clarifying some group B strep treatment choices. That was an episode 13 of season eight and we talked about in that one also timing of amniotomy and how GBS chemoprophylaxis works. And we discussed the scenario of a GBS unknown patient at term and under what circumstances you would still go ahead and empirically treat them. And one of the newer ones in the recommendations it was added a few years ago was if they had any kind of GBS positive result in a prior pregnancy and we said otherwise if they don't have a risk factor, gbs unknown patient should not be treated. But here we have this listener question. I'll read Dear OB, my pediatricians at the facility, I assume, interpret the current guidelines about unknown GBS as stating that we should treat the unknown GBS patient without risk factors unless we have a negative GBS NAT like a rapid GBS result, and this is based on the confusing table in the ACOG committee opinion number 797. Help signed GBS Blues in Boise.
Speaker 3:Those Idaho people? Well, yeah, so this is an issue. I think Table 1 in that committee opinion has a column, if you look at it, that says intrapartum GBS prophylaxis not indicated. That's the title and it has three sections. The first one is a maternal history of colonization during a previous pregnancy, which would not indicate automatic treatment unless the patient were unknown. So that's what you just mentioned. They had it before. They're unknown now, then you would treat.
Speaker 3:But if they have a negative culture, just because they had it before, you don't need to. The next one is, of course, if you had a negative swab obtained after 36 weeks in the current pregnancy that's the most common scenario or if you're performing a cesarean delivery before the onset of labor in a patient who has intact membranes. So we know those, we're good with all that. And then, of course, if you have a negative swab beyond 36 weeks but you have some of those risk factors such as labor let's say you're 36 and 5, but you had the negative swab, or you've had prolonged rupture of membranes as long as you have a negative vaginal rectal GBS culture, you still don't have to treat based upon risk factors. But the last one is the confusing one. So it says unknown GBS status at onset of labor, nat result negative and no intrapartum risk factors present. And that's where the confusion is.
Speaker 2:Yeah. So at first read it sounds like you need to satisfy all three conditions to be spared the antibiotics being GBS unknown and having the negative rapid test, nat or NT and, by the way, that's not the same thing as being GBS culture negative. You're still unknown even if you have the negative rapid test. So unknown, negative test and no risk factors present. So they're using and instead of or, and so we can see how someone would say you have to have all three, or else you're supposed to give antibiotics if any one of those things is missing.
Speaker 3:Exactly and you can tell that the NAT testing was added into this table after some editing. It's relatively new, maybe hastily, this wasn't edited well. I think it does say in the parallel column that a negative NAT does not overrule risk factors. That is, if there's no culture or result, you treat for risk factors even if they come up with a negative NAT. So like if you have a GBS negative culture at 36 and you come in labor at 36 and five, that preterm birth is a risk factor.
Speaker 3:But if you had a negative NAT at 36 weeks and you came in and labor at 36 and five, you would actually treat there because a negative NAT isn't good enough to overrule a risk factor, whereas a culture is of course other than fever. So that should help you understand that. The interpretation of the text in the parallel column we're focusing on how NAT works into this, in that if you have a negative NAT you have to also not have risk factors is what they're saying in that column and it's just confusing the way it was added in. If there's a positive NAT and or if there's risk factors, you should treat as a way of thinking about that If you read the text of the document and not just the tables, then this is the obvious interpretation.
Speaker 2:Okay, yeah, so I'll read the relevant passage out now. If the prenatal GBS culture result is unknown when labor starts. If the prenatal GBS culture result is unknown when labor starts, intrapartum antibiotic prophylaxis is indicated for women who have risk factors for GBS early onset disease. At-risk women include those who present in labor with a substantial risk of preterm birth, those who have preterm pre-labor rupture of membranes or rupture of membranes for 18 hours or more at term, or who present with intrapartum fever. So nowhere in the text does it say that there's a requirement to do the NAT test, and we were discussing offline. Many places don't have that available. I've never, ever, had it available. I've worked in a lot of different places and I think you said you don't really have it available either.
Speaker 3:Well, there's been a big point of emphasis about the NAT test and for institutions that choose to do those, there are lots of reminders in here for them about how to use it appropriately. It's not a replacement for the culture. For example, it doesn't override risk factors. If she develops one of those intrapartum risk factors, you should still give antibiotics because the sensitivity of NAT is too low to exclude treatment for those risk factors. It's not a culture and shouldn't be interpreted. There's still GBS unknown even though the NAT is negative, and that's a key part there. The enrichment, incubation step of a normal GBS culture, which takes time, is important for the enhanced sensitivity of a culture as compared to the NAT test. So this stuff was added in and there's a lot of emphasis on making sure that people don't over-rely on the NAT or misuse the NAT test.
Speaker 2:The CDC and the American Academy of Pediatrics agree and refer to the ACOG committee opinion for their treatment recommendations as well. But if anyone still is questioning this and wants to interpret that one bullet point in that committee opinion in the most conservative way possible, then I'll point out there is an official mobile app from the CDC called PreventGBS and this is endorsed by ACOG and the American College of Nurse Midwives and it has algorithms that walk you through scenarios both for obstetric and for neonatal providers. So if we go to this app and click on obstetric providers then it'll ask a series of questions. We'll give this hypothetical case here.
Speaker 2:Did the patient have a previous infant with invasive GBS disease? No. Was GBS isolated from the urine at any time during this pregnancy? No. Anticipated mode of birth Faginal Gestational age 37 weeks or greater. Are results from a prenatal GBS screening available no. So that makes some GBS unknown. Gbs screen available no, so that makes them GBS unknown. The next question is did the patient have prolonged membrane rupture or a fever? No. Are results from an intrapartum GBS screen available? So that's the NAT test. Then we'd say no, so that running through that then it spits out the recommendation of GBS prophylaxis not indicated at this time.
Speaker 3:Yeah, and that's really the best way to show folks who are questioning this. This is the CDC guideline and it takes away. It's not unambiguous. This isn't really controversial, so if people are interpreting it in a different way, they just need to be educated about this misunderstanding and shown that there's a lot of variation out there in the real world and how pediatricians treat these various scenarios and, in particular, how long they'll monitor a newborn under different scenarios that come up. In fact, there's so much variation that the American Academy of Pediatrics published in 2019 a new bulletin called Management of Infants at Risk for Group-Bestructed Coggle Disease, and I'll put a link to it. Called Management of Infants at Risk for Group Distrupted Coggle Disease, and I'll put a link to it. They claim that this document clarifies a lot of the previous uncertainties in management that pediatricians were faced with, and I'll say I read it three times and it's, I won't say poorly written, but it's not clearly written and, honestly, it doesn't really clarify much. It still has too much vagary in it for my taste. The areas where you see variation in management of the newborn include this situation where a woman who is GBS unknown and receives no treatment because she had no risk factors where she has a newborn, and now the pediatrician has to decide how long to monitor that newborn and in what way. So I think we see a lot of 48-hour monitoring, as if it was a GBS positive pregnancy that didn't receive adequate treatment. And then you might see variation in how that monitoring, what it looks like, where pediatricians might do a blood culture, they might do a CBC, they might do a C-reactive protein and some might even do empiric antibiotics even though the newborn really has no symptoms. So part of the confusion is that the pediatricians universally haven't decided on a best approach.
Speaker 3:The document provides three current approaches for risk assessment for infants born at greater than 35 weeks gestation. So one is called a categorical risk assessment, another is use of a neonatal early onset sepsis calculator and another one they call enhanced observation. So you can take a look at these and you can run through these algorithms, but let's do it for this situation where a GBS unknown mother with no risk factors didn't receive antibiotics and has a healthy, appearing newborn. So for the categorical risk assessment option that first one there's an algorithm and the first question is are there signs of clinical illness? And of course, for all these, if there are signs of clinical illness. Well, yeah, then your treatment is blood cultures and empiric antibiotics, but that part's straightforward. But if there's no signs of clinical illness, then the next question is was there a maternal fever? Again, for all those situations in which there there a maternal fever, again, for all those situations in which there was a maternal fever, regardless of whether or not there was GBS chemoprophylaxis, the treatment is still going to be blood cultures and empiric antibiotics. Okay, but in our case we have a newborn with no signs of clinical illness. There was no maternal fever.
Speaker 3:And the next question is was GBS intrapartum antibiotics indicated for the mother? And this is the stickler. This is why this question is was GBS intrapartum antibiotics indicated for the mother? And this is the stickler. This is why this question is coming up and why it's important to understand that this scenario. There wasn't an indication. Our answer is no. But if you interpret the answer is yes and that the obstetrician should have given antibiotics over a misunderstanding of this guideline, then yeah, the appropriate management would be clinical observation for 36 to 48 hours after birth. But if the answer is no, which it is, in other words, antibiotics were not indicated and they weren't given then it's routine care, which means again, all things being normal, discharged the next day absent any signs of clinical illness.
Speaker 2:Yeah. So the critical decision point here that's been raised in this listener question is whether or not these antibiotics were indicated in this GBS. Unknown mother, low risk, healthy baby. So understanding the proper interpretation of the ACOG guideline is essential for that, and it'll be the difference in whether these babies are kept an extra day, perhaps for no reason.
Speaker 3:Right. I said there's two other things. There's also the enhanced observation option, and this one's a little bit simpler. It just asks if there's signs of clinical illness. If no, the next question is whether there's fever or inadequate indicated. Again the same issue GBS chemoprophylaxis. If the answer is no, then again routine care, which includes next day discharge perhaps. But if the answer is yes, then serial exams and vitals for 48 hours and culture and perhaps empiric antibiotics if the child doesn't look well. So again, the critical question is whether or not these antibiotics were indicated, because it drives you down the other side of these pathways.
Speaker 3:Now the other approach is using this early onset sepsis calculator, which I had a lot of fun playing with. I'll put a link to it. It's really interesting and this was developed by Kaiser Permanente, and basically you put in the very specific data about the patient in the calculator and then the calculator spits out the recommendation for the pediatrician. So I've played around with this. You can put in all sorts of scenarios. It's very interesting. It asks you to select the incidence of early onset GBS sepsis in your community and then you put in the gestational age and the highest maternal temperature during her labor and, if you don't know your local incidence, which I certainly don't then you put in the CDC national average.
Speaker 3:If we put in that national average and then we say that the patients say 37 weeks and five days, that might be the kind of scenario where somebody shows that before their swab is resulted and her screen you put in not resulted yet or unknown.
Speaker 3:And then let's say that the highest maternal temperature is 99 degrees Fahrenheit and that our water was ruptured for six hours. And then it says if the child is well appearing, then no cultures and no antibiotics are indicated. Any discharge after 24 hours is appropriate. So it calculates the incidence of early onset GBS disease in that specific scenario as 0.22 per 1000. And if the child is well appearing, the incidence is 0.09 per 1000. So that newborn should go home the next day for the untreated GBS, unknown mother without risk factors and an unknown NAT result, as long as it's well-appearing. Regardless of which of these three decision-making methods you use the calculator or the other two algorithm based approaches the GBS, the infant of a GBS and known mother with no risk factors who's well-appearing, is a candidate to go home on the first day of life. And that's the clinical difference that we're seeing and they don't need enhanced observation.
Speaker 2:Yeah, that calculator is interesting to play around with and you can put in lots of different scenarios and see how they impact the GBS early-onset disease risk and get a sense of the actual numbers that we're talking about. We have a tendency to magnify risk and not understand how these various risk factors affect the total absolute risk. But the calculator gives you real numbers, so it's definitely a helpful tool and, more importantly, it gives direct guidance about how the pediatricians are supposed to be managing these scenarios if they choose to use that algorithm. But by all three different algorithms that the AAP lays out as options, the newborn of a GBS unknown mother who didn't get antibiotics and had no risk factors, and who the newborn is developing, should be treated normally and go home as early as the next day. So it really makes you question the value of doing the NAT at all, and that might be why a lot of facilities don't utilize it.
Speaker 3:Yeah, it's hard to think of where it changes management for the mother or the newborn. All right, well, you appreciated our cesarean hysterectomy episode.
Speaker 2:I loved it. It was so great.
Speaker 3:You were sunning in Finland.
Speaker 2:Yeah, I got such a tan with the zero sunlight.
Speaker 3:And we'll be back with another guest next episode and talking about advanced maternal life support. So something to look forward to in a couple of weeks.
Speaker 2:All right.
Speaker 3:All right, we'll see you then.
Speaker 1:Thanks for listening. Be sure to check out thinkingaboutobgyncom for more information and be sure to follow us on Instagram. We'll be back in two weeks.