Episode 8.8 Finding Clinical Answers, Iron, Fetal Testing, and Steroids
In this episode, we discuss four tips for finding evidence based answers quickly. Then we discuss some new literature about pap smears and new guidelines regarding iron supplementation in pregnancy. We also discuss the history of corticosteroids for fetal maturity and the hype cycle in medicine.
00:00:02 Finding Evidence-Based Clinical Answers Quickly
00:13:36 Understanding Evidence-Based Clinical Practice
00:23:30 Cervical Cancer Screening During Pandemic
00:33:51 Optimal Timing for Cervical Cancer Prevention
00:40:12 Iron Supplementation in Pregnancy
00:47:13 Corticosteroids and Hype in Medicine
Links Discussed
Cervical Cancer Screening Rates Among Rural and Urban Females, From 2019 to 2022
Population-Based Incidence of Cervical Intraepithelial Neoplasia Across 14 Years of HPV Vaccination
Optimal Timing of Delivery for Pregnant Individuals With Mild Chronic Hypertension
Screening and Supplementation for Iron Deficiency and Iron Deficiency Anemia During Pregnancy
What we have learned about antenatal corticosteroid regimens
Transcript
Announcer: 0:02
This is Thinking About OB-GYN with your hosts Antonia Roberts and Howard Herrell.
Howard: 0:18
Antonia.
Antonia: 0:19
Howard.
Howard: 0:19
What are we thinking about on today’s episode?
Antonia: 0:21
Well, we’re going to go over a few articles and we have another four tips segment again and an exciting history segment as well, but I need to remind you this right now is our 99th episode, so you know what that means, right.
Howard: 0:35
Oh yeah, okay, so we’re flipping next time.
Antonia: 0:38
Yeah, that’s right. So tune into the next episode and find out what’s different.
Howard: 0:42
We’re real interesting people, aren’t we?
Antonia: 0:46
It’ll just, it’ll be totally mind boggling.
Howard: 0:49
Yeah, I’m sure Well it’s been a long time coming.
Antonia: 0:58
Well, I’m excited to finally make a little switch. All right, all right, well, okay. So we have four tips for the daily practice of finding a clinical answer that’s evidence-based, quickly and efficiently. Now, these tips will vary on the kind of question that you’re dealing with. So our first tip is, if you’re looking for a general medical question that’s outside of your normal specialty, then do a Google search for the symptom or disease you’re interested in, plus the letters AAFP. So, for example, abdominal pain. AAFP gives me an article in the American Family Physician Journal titled acute abdominal pain in adults evaluation and diagnosis from 2023. Now, for me, this article is behind a paywall and I would have to pay $165 for to get a year of access, which I haven’t done. But, frankly, AAFP’s articles they would probably be worth it because they put out some pretty good summaries of almost any basic kind of clinical topic. But, of course, if you can qualify for some kind of discounted maybe a student or a resident access or a departmental subscription, then definitely take advantage of that.
Howard: 2:02
Yeah, and that only applies to the articles that were published in the past year. So you picked one published in the last 12 months, but if it was more than 12 months old, the article is completely free, so it’s actually unusual that you run into the paywall. But definitely $165 is less than we pay for a New England Journal subscription or a lot of other things and I use this resource all the time. And obviously OB-GYN patients who have we see them. They have lots of different complaints that aren’t specifically in our obstetrics and gynecology bailiwick and it’s always a good idea to look up those complaints or conditions to see what the latest treatment or evidence is and make sure we’re providing up-to-date and evidence-based care.
Antonia: 2:40
So hold on for a second bailiwick.
Howard: 2:42
Yeah, bailiwick, it’s like your wheelhouse, your turf or province or your ambit.
Antonia: 2:46
What’s ambit? Did someone give you a thesaurus or something?
Howard: 2:50
Okay, how about scope?
Antonia: 2:51
Scope Okay, fine, I’m good with that.
Howard: 2:53
Okay, well, for things that are out of my scope, like, let’s say, I see a patient who has pink eye when I shouldn’t, or what medications or treatments are appropriate. So I can go Google pink eye plus AFP, and an article from the American Academy of Family Practice will pop up that’s evidence-based and peer-reviewed. It’s usually fairly short. It has all the good things like a differential diagnosis and pictures. Medications usually their relative prices, so you know which ones are more and less expensive, algorithms for workup, red flag symptoms, other things like that, and in three or four minutes or five at the top, I can become pretty up to date and provide evidence based care for these sorts of conditions that I don’t see every day. And again, all of them are free, except for those like you found published in the last 12 months and you need a subscription for that, and you’d need a subscription for that. And if you don’t want to see that 2023 version of abdominal pain, you can scroll down and you can find the older 2008 version and get it for free too.
Antonia: 3:50
Yeah, that’s definitely helpful to know. I’m sure there hasn’t been too much that’s really changed about abdominal pain in the last couple of decades, but I think a lot of people already have up-to-date subscriptions and tend to use up-to-date for this purpose.
Howard: 4:05
Sure, and there’s lots of these general databases, but honestly, the AFP articles are more scholarly and more evidence-based and written with less bias than almost anything else you’re going to find, and they’re just as reader-friendly and visually as our favorite, the RCOG Green Top Guidelines that we’ve talked about before.
Howard: 4:21
Up-to-date articles are usually too long, and sometimes they’re just difficult to get the answer you need quickly. A lot of those articles are written by people who want to influence their field, and so they’re not often as balanced as they maybe could be. But up-to-date can serve a purpose to fill in gaps where AFP doesn’t have a current article or the article is rare or something like that about a topic that’s rare. You can also use Dynamed for this and honestly, dynamed is a little more navigatable than up-to-date is.
Antonia: 4:47
All right. So that first tip was just regarding general field of knowledge type questions where you’re getting a broad overview and you’re quickly getting down to some practical points of treatment. But that’s not typically the sorts of things that we talk about here on this podcast. We tend to get deep into the weeds on questions. That sort of quick search doesn’t really satisfy, Like an AAFP article wouldn’t satisfy a lot of our topics. So what if you have a specific question about a very specific type of treatment for someone that has very unique risk factors? How would we go about finding something more targeted for them?
Howard: 5:31
Sure, and I do this every day too, not just for the podcast but just for clinical practice. So for this we want to do what’s called a PICO search. Pico is an initialism, the P stands for patient, population or problem, the I for intervention, the C for comparison and the O for outcome. You can do this search directly in PubMed or it’s also neat to do it in something like the TRIP database. If you’ve not checked out tripdatabase.com, you might be interested in their service and honestly, that’s worth the subscription, which isn’t that much, and they didn’t pay us to say that we have no advertisers. But if you’re listening, Tripp, you can pay us. Anyway, I might structure a search like I have a patient with endometriosis and I’m considering ablation of lesions versus peritoneal stripping for relief of pain.
Howard: 6:13
So there I have to define the population and the intervention with the comparator and then the outcome I’m interested in. So you can enter that into the fields on the Tripp database directly or even just type it into PubMed something like endometriosis, ablation, stripping pain and you could add to that the type of study you’re interested in, either using a filter in PubMed to select randomized, controlled trials or some other type of study, for example. So those types of searches will get you into the literature and help you start to answer very specific questions. But then of course be careful that you look through lots of the articles or links that come up, not just the first couple of hits or the first one or two that you see that satisfies you.
Antonia: 6:50
Okay, so I just tried that in the Trip database search engine and it provided 11 articles, most of which are review articles, but, honestly, about seven or eight of them look like they’re exactly what we would need to look at to understand more.
Howard: 7:06
Yeah, and when I did the same search terms that I just said in PubMed, I only got six hits and only a couple of those looked very relevant. So try both databases, but learn to structure questions in a way that will help you find helpful results, and that’s what the point of PICO is.
Antonia: 7:22
Okay. So then the third tip, or quick evidence-based answers, is just to be familiar with the point of care apps that you can get for your phone or mobile device that are relevant to your specialty. So for us that would include the ASCCP app for management of abnormal pap smears and colposcopy results, then the ACOG app we use that a lot for well a lot of things, but especially looking up when is delivery indicated for a certain medical issue. They’ve also got a nice little pregnancy dating portion in their app and some other stuff. The LactRx app it used to be called the LactMed app helps you look up safety of drugs, mainly for breastfeeding, in a limited sense also for pregnancy.
Antonia: 8:07
Then there’s the USPSTF app that has screening guidelines for mainly, like I’d say, routine primary care, but you want to look there for breast cancer screening guidelines, colonoscopy screening, for example. Then there’s the NCCN app for cancer and pre-malignant cancer screening guidelines, and so I would use it, especially when someone gives me a certain family history of a certain type of cancer, to see if these guidelines say they should get genetic testing or counseling. And, of course, if you’re a resident on your GYN oncology rotation or any type of oncology rotation you might have. You’ll definitely need the NCCN app and then there’s a few more. There’s the CDC MEC app for birth control. You’re running a patient’s medical conditions against this app and see what birth controls they should or shouldn’t use.
Antonia: 8:59
And then you’ll want to have some kind of general drug reference like epocrates or Micromedex or maybe even use up to date when you want to look up kind of general drug reference like epocrates or micrometics or maybe even use up to date when you want to look up things like what’s dosing, what’s the half-life, what’s the excretion and metabolism and drug interactions and all those kinds of things just on the fly yeah, and there’s a lot of these menopro from the north American menopause society, which I think is not currently being updated, unfortunately, but a lot of folks will use that one, the SEDTX guide from the CDC and, of course, most of those references we already mentioned, like UpToDate or Dynamed, they have apps for your phone or tablet as well, so we’ll be sure to put some of these apps on the Instagram, and if anybody has others that we didn’t mention that you find useful, leave a comment on that post and we’ll all get to see them.
Antonia: 9:43
Yeah, and of course having more and more stuff on the phone doesn’t exactly help someone who’s maybe looking at their phone too much. Anyway, I look at my phone way too much, I think. So I’ve also got the remote access to the health record, and so that’s something I can pull up if I’m on the go and I can’t even sit down at a computer to look at patients.
Howard: 10:03
Yeah, sometimes you just have to unplug, but there’s seemingly infinite medical knowledge out there and these apps aren’t a substitute, obviously, for good clinical reasoning and judgment and treating patients with dignity and encompassing all of their needs holistically. Ai can’t replace doctors, but hopefully someday it can help minimize a lot of our repetitive, mundane, busy work and help us with our blind spots and things like that. We have to be diligent to stay up on top of our education and if you listen to our podcast regularly, that’s maybe one of your reasons why you do it. But then use these apps in an appropriate and efficient way to aid in patient care and maybe it saves us time and improves quality of lives for our patients and for ourselves.
Antonia: 10:40
Yeah, and sometimes I think using these apps actively together with a patient and talking them through what am I looking at here? What am I doing? Reading out what I’ve got on there may add a little bit of weight and credibility to things that they might be wondering about or questioning. Like if I say this is my reference for this question that you’re asking me about, can you take this drug while breastfeeding, for example? For this question that you’re asking me about, can you take this drug while breastfeeding, for example? Well, at least I hope it adds a little credibility, but usually I just can’t tell them. Off the top of my head. There’s this much data or this little data about some random thing they’ve asked.
Howard: 11:16
Okay, and patients value providers who do look things up. There’s a lot to know out there and never be embarrassed by saying that you don’t know something and finding the answer the patient needs.
Antonia: 11:27
Well, our last tip, then, is what you said be familiar with the various guidelines in your field. So this might be more something to try to internalize rather than just rely on your phone or, at a minimum, know where you can access a guideline very quickly. So either subscribe to the journal itself or subscribe to maybe some regular email updates from your professional societies. So whenever you open your inbox you have like, oh, they just updated labor management or something like that, and of course, then also follow these guidelines in your practice. That’s what really helps you internalize them, and if you don’t, then make sure you can defend why you don’t follow these guidelines. But even for general OBGYNs in the US, this is going to be more than just ACOG guidelines. I’m sure most of the listeners are familiar with the different documents that ACOG produces, which do function as guidelines, but many of what we look to for how to practice and what’s the standard of care come from a lot of other sources as well.
Howard: 12:27
Yeah, so we have guidelines from the CDC, the US Preventive Services Task Force, obviously ACOG, but also things from the Society for Paternal Fetal Medicine or the North American Menopause Society or any of our subspecialty professional groups, and for more general medical problems these guidelines could come from the AAFP, the American Medical Association, really anywhere.
Howard: 12:47
I also find it very useful a lot of times to read Canadian and European guidelines for our OBGYN societies. There we mentioned again those Royal College guidelines, which are really quite wonderful in the way they’re structured and the way they’re written, and then understanding how our guidelines differ from theirs and why perhaps, is very educational. But the general tip here is simply to Google the word guideline plus whatever topic you’re interested in, like, say, cervical cancer screening, and this strategy works pretty well just doing that. I just did that for cervical cancer screening and the first guideline that came up was in fact from ACOG, and then the guideline from the US Preventive Services Task Force and then the American Cancer Society, the National Cancer Institute, the CDC, the ASCCP, the AAFP and others come up. So this strategy works well for most things that actually have a guideline associated with them.
Antonia: 13:36
All right. Well, these are the sorts of things that we use every day in clinical practice and also that we talk about on this podcast. So we encourage learners and residents to use these searches daily, and the more you do that, the better you’ll become at either just remembering them or remembering how to find them really quickly and efficiently, and you’ll start to just be able to rattle it off. This, in some ways, it’s not just memory, like remembering facts, it almost becomes like a muscle memory, and then sometimes, when you have a little bit more time to look something up, then it’s really helpful to know what are the best, what resources have served you the best in the past, and then you can get really educated in something that maybe is particularly interesting to you. But we can talk more about that on a different day, I suppose.
Howard: 14:23
All right. Well, let’s see how many recent articles we can get through in a blurry.
Antonia: 14:27
All right, let’s go.
Howard: 14:28
All right. Well, there was an article back in April 2024 in the Journal of Maternal, Fetal and Neonatal Medicine that looked at the cost effectiveness of antenatal fetal surveillance monitoring for medication-treated gestational diabetes. Now the current guidance from ACOG is that antenatal fetal testing be started on gestational diabetics who require medications insulin whatever starting at 32 weeks. We keep talking about some of these antenatal testing recommendations and we need to spend a whole episode on that at some point, but most of them have not been directly validated in clinical trials as to whether or not they improve outcomes.
Antonia: 15:02
Yeah, and this is one of the things I’ve seen most aggressively monitored, like twice weekly, and the testing in most cases for this, just like for any other indication, is just recommended for patients who have a certain risk of fetal demise, where in theory that antenatal testing might be beneficial to catch some early sign of distress and prevent the fetal demise by delivering them early. In theory, but in practice these have not been the subject of randomized controlled trials and there’s at least fair evidence that in many cases the testing really makes no difference. There’s going to be a fetal demise A lot of times. This doesn’t catch or prevent any of that. For example, cholestasis of pregnancy or maternal obesity, as we’ve discussed before. It hasn’t shown to reduce the demises there either.
Howard: 15:51
Yeah, it depends on the etiology of the demise.
Howard: 15:54
A lot of fetal demises associated with diabetes are due to just excursions in blood sugar that are temporary and high, and not something that you’re catching on the day of testing, because it happens three days later and there you go, and so testing can’t predict that the blood sugars are going to be 300 for a sustained period of time two days later.
Howard: 16:12
But it can find pregnancies with placental insufficiency and things like that that develop slowly over time. So we should talk more about that later. But in this study they included 652 pregnancies, and the limitation of this study, like a lot of these studies, is that there just weren’t any stillbirths in the study. Now they did deliver 12 pregnancies earlier for abnormal biophysical profiles, but all of those were after 36 weeks. Of course, we don’t know that any of those deliveries actually prevented anything right. Was that going to be a demise that they prevented by doing the earlier delivery? We don’t know, and this is retrospective data, but the point is they didn’t find any actionable test results among all the 652 patients that they tested until at least after 36 weeks of gestation.
Antonia: 16:57
Okay. So if we were going to look at that and then talk about excluding the tests before 36 weeks, since they didn’t find anything actionable, that would still save what over 2000 tests just in this study population, and that would cost probably close to $200,000.
Howard: 17:15
Yeah, they said for these particular panel of patients, 2041 tests not done between 32 and 36 weeks and their average cost, which reflects your payer mix too, but it was about $186,000. And that’s just direct costs and that doesn’t include the indirect costs of lost productivity or paying for childcare or other expenses that the patient may incur to take time off from work and go to these visits which seem unnecessary.
Antonia: 17:41
Well, like a lot of the ones we’ve discussed already, it’s up to really the Society of Maternal Fetal Medicine to maybe change the recommendations about this extra testing. But it seems safe to say that there’s no evidence, at least, that testing is beneficial until 36 weeks for diabetics. This year was medication-controlled diabetics.
Howard: 18:07
Yeah, gestational diet-controlled diabetics. We’re not talking about type 1, type 2, pre-existing diabetes. We’re talking about a gestational diabetic who happens to be on a little bit of insulin or something. Okay, here’s another one. We’ve talked about anti-malarian hormone before, back when we discussed fertility, and this is a test that’s being widely maybe misused or at least misunderstood by physicians who order it and the patients who have it performed, and now it’s even being marketed direct to consumer through apps.
Howard: 18:35
I see ads on Facebook and other special fertility workups and evaluations at based medicine that we’re seeing an explosion of marketed towards women who were trying to get pregnant and they’re told that they need to do this test and maybe some other hormones or things like that. But there was a study, also from March of 2024 that was published in Human Reproduction, and this was an interesting study design. Basically, they gave patients some evidence-based information, a little brochure about what anti-malarian hormone tests actually mean. It just answered short, simple questions with what the evidence means, and then they saw how that influenced the patient’s choice to have the test performed, as compared to what they read about the test from a similar looking brochure, but with evidence or statements from an online company who were selling this test directly to consumers and basically they found that when women who viewed the evidence-based information, they had a significantly lower interest in having the test performed when they were told the truth.
Antonia: 19:35
I’m sure that same effect could be observed with a lot of different tests and maybe interventions that we offer too, but for AMH I think that decreased interest after knowing what the evidence is really shouldn’t be a surprise.
Antonia: 19:52
But I think it’s not just the online companies that are making this test sound like something it isn’t. They actually linked a nice five-page PDF within this study that has the information that they provided to patients, and I think in Australia this test is not covered by insurance, so knowing the utility of this test is that much more important for patients who are going to have to pay for it. But the evidence-based information says explicitly it’s not a reliable test of fertility and it cannot tell you the chances of getting pregnant, nor can it tell you when is a patient likely to reach menopause. This study also used a pamphlet of essentially misinformation. It was just taken straight from one of these company websites that sells direct to consumer, and this pamphlet said AMH could tell a woman how many eggs she has left, what’s her likelihood of conceiving, and that it was useful in evaluating the current fertility status and may predict the onset of menopause. And all these things, of course, are not true, but that pamphlet made it seem a lot more enticing to have it done.
Howard: 21:03
Yeah, and physicians are making some of those same claims. So it’s important for general OBGYNs in particular to know that AMH is just not what it’s being marketed, as I think, and I think we learn a lot from what we see on social media as well, and so if you’re seeing companies market this on, you’re going to have patients come in and ask, and so it’s important to. There’s so much medical misinformation and disinformation on the internet about so many topics and many of these companies or predatory groups. They prey upon patients’ fears and anxieties and, as we’ve discussed before, for fertility and subfertility, this definitely creates a situation that’s ripe for exploitation of vulnerable patients.
Howard: 21:44
But this sort of bad information is all over the internet about all sorts of topics, ranging, of course, from birth control and all the garbage on TikTok to nutrition, to vaccine disinformation, but even misinformation about common diseases like polycystic ovary syndrome or endometriosis, and in many cases the bad information is perpetuated by folks who stand to make some money off of it. It’s usually started by someone who has something to sell. They’re not necessarily the ones repeating it. You see it echoed all over the internet, but some reproductive endocrinologists out there. They make claims about the AMH test and it might serve a purpose, intentionally or unintentionally, of scaring a patient more quickly into advanced interventions where there’s more money to be made. They might forego multiple cycles of ovulation induction in favor of more aggressive treatments because they’ve been wrongly influenced by the AMH test.
Antonia: 22:38
Well, and that’s pretty crazy, because a low AMH predicts a poor response to IVF. So those should be the patients who do more ovulation induction instead, right, instead of going the more expensive IVF route that has a much lower chance of succeeding for them making one egg with letrozole, for example, as anyone else. Anyway, that article and those materials they showed the patients are not behind a firewall, so if folks want to take a look, then you should go ahead.
Howard: 23:12
Yeah, we’ll put our Instagram ninja on this one. It’d be nice to take the points that they made that contain evidence-based information about anti-Mullerian hormone and maybe put that on Instagram and you can share that with your patients as well. We really do have to work in TikTok and social media about putting out good information.
Antonia: 23:28
Yeah, okay, next one. There was another article in the June 14th edition of the JAMA Network, open, entitled Cervical Cancer Screening Rates Among Rural and Urban Females from 2019 to 2022. So pandemic times, and they sought to ask the question of whether pap testing rates changed among rural and urban females during the COVID-19 pandemic, and so they looked at some cross-sectional surveys and found that in 2022, only about 48% of rural and 64% of urban residents reported having received a pap within the past year, and these rates were about 70% lower than they had been in the three years prior to the study, which was their starting data before the pandemic. So from this newer data, they concluded that the pandemic had a negative effect on cervical cancer screening.
Howard: 24:27
Yeah, I saw this article reported in some of the major media outlets distributed around as a negative commentary about how the pandemic had affected cervical cancer screening, and this was written by a couple of PhDs from the University of Kentucky, and they correctly comment that the incidence of cervical cancer screening seems to have declined. But then they have a call to action that we should be working on expanding access to get back to those pre-pandemic levels of cancer screening. But these sorts of articles are published in major journals all the time and they often miss the point entirely. So our literature is full of studies that take true data, real facts, and then draw completely inappropriate inferences.
Howard: 25:11
Now, the average age of the patient in this study was 43, meaning that the average patient in the study should have a cervical cancer screening or pap smear performed every five years. And so with that you would assume that about 20% of patients should report having had a pap in the prior year. And even if all the patients were under 30, well, okay, one every three years the number should still only be about a third of patients reporting a pap smear in the previous year. And of course the truth is there are many women who are under 21 or over 65, or maybe they’ve had a hysterectomy for benign indications and they shouldn’t be getting a pap anyway. But they then extrapolate this data point and this supposed problem that they found to 188 million women in the United States, so all the women in the United States, and that figure includes obviously a huge portion of women who are under 21 or over 65 and probably tens of millions of women who’ve had hysterectomies and otherwise don’t have an indication for a pap smear.
Antonia: 26:11
Yeah, so the decrease in the frequency of pap smears might be due to more providers getting on board with the evidence based guidelines about when paps should be performed.
Antonia: 26:21
This article really shows that too many patients are still getting excessive PAP smears. They probably should have asked about people having had a PAP within the last three years, or five years, more preferably than in the last one year. The gap between rural and urban PAP rates just shows that in rural areas, where patients tend to have less commercial insurance, there aren’t as many venture capitalist owned physician groups exploiting the insurances with yearly pap smears Because we know that, at least in our state, public insurance does not pay for it every single year. It’s actually shocking that two thirds of urban residents, many of whom do have commercial insurance, reported that they had a PAP within the past year. It’s hard to know exactly what that number should be, because it does include some patients under 30 and maybe some patients who should be getting them yearly if they’ve maybe had prior cervical dysplasia. But even at that, it couldn’t be correctly much more than 25% of patients that should have had a pap within the last year, given the demographics they reported.
Howard: 27:34
Right, and then the conclusion that we need to enhance cervical cancer screening based upon this burgeoning problem. That’s been manufactured. It’s just not correct. The truth is there probably are some patients who are not getting pap smears due to lack of access, but the lack of access is ironically worsened by providers performing paps on patients who don’t need them. It takes up an unnecessary office visit slot, time slot and even if the patient is already there for an annual exam anyway, on a large scale the decision to do a PAP when it’s unnecessary still adds up to extra cost, either to insurers that could have gone to pay for better things, like an uninsured or underinsured patient getting the care that she needs, or it just gets passed down to the patient.
Howard: 28:20
But look for this pattern of articles in the literature that makes some claim a bold claim to prove the thesis which they set out, to prove that the pandemic worsened cancer screening but then misses the boat entirely. These sorts of counter narratives we talk about a lot with maternal mortality crisis and other things. The authors knew the guidelines, by the way, because they cite them in the paper, but it never occurred to them that pre and post pandemic patients were getting far too many pap smears. Both before the pandemic they were getting too many and even after the decline they’re still getting too many, per their own report.
Antonia: 28:55
Yeah, if they had been able to demonstrate that there was a higher rate of cervical cancer, then I might listen to their recommendation to increase screening. Well, this next article, I think, tries to get at that a little closer. The July 25th edition of JAMA Oncology looked at the population-based incidence of cervical intraepithelial neoplasia, not just from the pandemic but from across 14 years of HPV vaccination. So they know that over the last decade HPV vaccine in the US have increased and at the same time the rates of CIN per 100,000 screened women have dropped fairly dramatically, almost by two thirds in the population of women under 25 years old. And this drop is most pronounced in CIN one and two, but it’s also true of CIN three. And at the same time CIN has increased slightly in women over 25. They hypothesized that this increase was more likely due to an increased rate of diagnosis rather than true incidence. So that is because there’s increased reflex HPV testing over 25 that might lead to increased colposcopies and biopsies, and so you’re catching more CIN than you would have if you just did cytology alone and didn’t reflex to HPV.
Antonia: 30:24
Now, the last article we talked about had noted that most women over 30 in their data set were still receiving just a PAP and not HPV co-testing, and I still haven’t quite figured this one out. One of my theories of why providers might choose to omit the co-testing is that, well, maybe doing cytology alone it’s going to require more frequent visits, so they have to come back in three years instead of five years in the 30 and up age group, and that ends up being a nice, easy visit for them. It gives them that easy payout of whatever an annual visit pays out. Frankly, it’s a very minimal payout, really not enough that should motivate. Frankly, it’s a very minimal payout, really not enough that should motivate a clinic to try to squeeze more of those. That’s just my opinion, though.
Howard: 31:07
Well, but that’s not necessarily the accountant’s opinion. Technically, women should be coming back for annual visits anyway, but that doesn’t equal a pap smear?
Antonia: 31:18
Yeah, so that you should be.
Antonia: 31:19
They should be coming back anyway, even if they don’t need a pap.
Antonia: 31:23
And I remember in a prior episode you were talking about how, if we actually followed the WPSI guidelines for annual visits for women, those are meant to be pretty comprehensive, with lots of ground covered in much less time than what we’re given less time than what we’re given. So if we’re throwing extra PAPs into the mix because we’re not doing co-testing and we have to do PAPs more frequently, we’re really just making our own lives harder and doing a disservice to the patients. But we both know that a lot of women will skip their annuals even when they have access, especially when their lives are busy with career or kids and if they’re fairly healthy without any major complaints. So it might be that having knowing they have to have a pap maybe motivates them to come back in. I do see plenty of new annual guys who just haven’t had a pap in well over five years that they really should have, but they time just got away from them. They got busy for five plus years and just never came back.
Howard: 32:27
So, knowing that they need a pap every three years instead of five, even though it was normal, maybe some people think that that’s just a rationalization, that well, they’ll come back in three years under the assumption that she’s just going to skip other visits until she’s told she needs another pap.
Howard: 32:48
Although that’s de-emphasizing all the other, that just sounds like your annual exam wasn’t meaningful for the patient and all you focused on was cervical cancer screening if that’s the impression that patient gets and you’re not doing as good a job of testing for this CIN that you just mentioned by not doing the HPV testing it’s inferior.
Antonia: 33:02
And that logic does sound messed up. Another theory that I have is that there’s a fear that maybe the HPV co-testing won’t be covered by certain insurances, maybe even if it’s just one insurance company. So then the provider or group decides just to be safe, and so nobody possibly has a surprise bill for HPV. We’ll just make it a policy that we don’t do HPV on anyone, but to my understanding that’s not actually a thing, and I really can’t imagine that, even if someone did have to pay for HPV, that doing that every five years would somehow end up being more expensive than coming in for cytology alone every three years.
Howard: 33:46
Yeah, I don’t think that pain is an issue, If people have that impression they’re misguided.
Howard: 33:51
But we’ve had an uptake over the past decade and a half of HPV vaccination.
Howard: 33:56
Younger patients are just not seeing the bulk of HPV disease that they once did bulk of HPV disease that they once did and at the same time the HPV test itself is more sensitive and is better at catching disease than the cytology alone is.
Howard: 34:10
So the guidelines internationally are being updated as we speak and over the last few years and in the years to come to reflect this change in the disease. Even if the patient herself has not had the HPV vaccine, she still benefits from the population level uptake of vaccination because the had the HPV vaccine. She still benefits from the population level uptake of vaccination because the rates of HPV are declining in the population and therefore her sexual partner is likely to have either been vaccinated or to have had other sexual partners who were vaccinated. So for people really passionate about preventing cervical cancer, they don’t need to be emphasizing pap smears, they need to be emphasizing HPV vaccination in both young boys and girls. And we can eliminate cervical cancer and a lot of other cancers with effective vaccination programs, and Australia is a good case study of this, if anyone’s interested.
Antonia: 34:56
I do love how the same parent publisher, JAMA, will frequently publish articles that are going in completely different directions with the different journals they own, like saying how these last two studies we talked about like people need to have more yearly PAPs, and then, on the other side, like get HPV vaccines so you can have less PAPs. It’s like the left hand doesn’t know what the right hand is doing.
Howard: 35:21
Well, less PAP smears is a good thing and more HPV vaccination is a good thing, so I think that’s the bottom line of both of these articles.
Antonia: 35:28
Well, we’ll go on to the next one. In September 2024 in the Green Journal there was an important new trial published that tried to determine optimal timing of delivery for pregnant patients with mild chronic hypertension pregnant patients with mild chronic hypertension. So currently ACOG recommends a pretty broad range for delivery timing. So for people with this condition they can go as early as 37 weeks and as late as 39 full weeks, like 39 plus six weeks for patients with chronic hypertension. And within that wide range you may see a lot of obstetricians trying to lean towards delivering everybody at the 37 to 38 week mark because that seems to give a little more leeway, reduce any possible incidental fetal demises that might have happened, maybe allow wiggle room if they have to get deferred for another few days if the hospital is full, and so then they would rather err on the side of delivering a little earlier within that range than delivering later.
Howard: 36:32
Yeah. So in this study they looked at the outcomes through a planned secondary analysis of the previously published CHAP trial, which I think we discussed a couple of years ago. So this included patients who had a new diagnosis of chronic hypertension during the first half of the pregnancy, as well as patients who entered pregnancy knowing that they had hypertension as a preexisting diagnosis. That was about 22% of them were new diagnoses and 78% had hypertension when they came to the OB’s office. Now, if you remember, these patients were randomized to treatment for lower blood pressure targets than maintaining, that is, being below 140 over 90, versus the previous sort of management where we were okay if their pressures were as high as 160 over 105.
Howard: 37:16
And this paper was really the reason that made the case for giving treatment during hypertension. But in this secondary analysis they found that planned deliveries at 37 weeks of gestation was associated with a 2.7 adjusted odds ratio of respiratory distress syndrome and delivery between 37 and 38 weeks was also associated with nearly double the rate of neonatal hypoglycemia. And they concluded that planned delivery in the early term period, compared with expected management up to 39 weeks, was not associated with a reduction in adverse maternal outcomes but was associated with an increased risk of some of these neonatal complications and they recommended really reconsidering when we should do most of these deliveries and that they should probably be around 39 weeks, with individualization for patients with added risk factors perhaps.
Antonia: 38:06
Yeah, they didn’t comment on differences in the rates of cesarean or modes of delivery period. Though there were numerically more diagnoses of preeclampsia in the patients expectantly managed, this wasn’t consequential and the combined maternal aggregate outcome was not statistically different among the two groups. And I do think sometimes there’s a cavalier attitude about clearing the deck, if you will, of all the high-risk patients. Get them delivered as soon as possible, particularly in busy centers, and there’s probably a sense that this reduces liability for those possible rare fetal demises and things like that, and it feels like the right thing to do sometimes. Just get them delivered as soon as possible if they have a medical problem. But if we’re just doing everyone at 37 and zero whenever there’s a wide range that starts at 37 and zero, we may just be putting more babies in the NICU for no good reason.
Howard: 39:07
Yeah, okay, well, speaking of guidelines and evidence-based practice, the other new publication recently that came out that was a major update to our guidelines was regarding iron supplementation during pregnancy. Now, we’ve talked about this topic before in some of the literature that supports or doesn’t support routine iron supplementation, but there’s a new US Preventive Services Task Force guideline that was just published.
Antonia: 39:31
Yeah, this is actually in JAMA in the August 20th 2024 edition and it comes from the USPSTF and it’s entitled Screening and Supplementation for Iron Deficiency and Iron Deficiency Anemia During Pregnancy. Basically, they conclude that the current evidence is insufficient to recommend screening for iron deficiency or iron deficiency anemia during pregnancy, and concludes that it’s also insufficient to recommend routine supplementation of iron during pregnancy.
Howard: 40:06
So the question about iron has been around for a long time and we’ve discussed some of this again previously. The main problem is that all of our CBCs they have parameters for normal on them that really are 200-pound white males, not for volume-expanded and physiologically diluted pregnant patients. So the first question is when is a pregnant patient actually anemic? And most people think that their hemoglobin needs to be less than, say, 10.5, but there’s a debate that ranges from 10 to 11, and maybe it matters by which trimester she’s in. But we don’t have a good normalized range for pregnant patients, certainly not.
Howard: 40:46
That’s printed out on those lab results. But you know practically what happens is that when that little red number pops up on the screen, patients are routinely told that they’re iron deficient, as if iron deficiency is the only cause of anemia. By the way, the other thing that happens is that some physicians will universally check iron levels in pregnancy because they assume that iron deficiency is this common and rampant problem. So I don’t think any of this is saying that if your newly pregnant patient comes in and she has prenatal labs and her hemoglobin is 9.8 and she has a mean corpuscular volume lower than 80, that you shouldn’t consider iron studies or iron supplementation. That’s not the point at all. But the idea that there’s some benefit for the majority of women who are pregnant in getting their hemoglobins higher than 11 or 10 and a half or whatever, by some super supplementation of iron is just not based in evidence.
Antonia: 41:43
Yeah, and there’s not even a truly good reason for prenatal vitamins to routinely have iron in them. And we know some of them don’t, especially the gummies, because it’s not practical to get iron into gummy form and the iron is a frequent source of constipation and nausea and other undesirable side effects. So it might actually make it harder for them to even take the prenatal and then they end up having less folate supplementation because we’re adding in iron that they don’t even need. They do comment in this paper on the WIC program and they note that so many women have frequent hemoglobin check at the WIC office. That’s women and children. It’s like a supplemental assistance program and this seems to be largely nonproductive. But it is frustrating to get calls or notes from the WIC office that your patient is anemic in quotes when their hemoglobin is 10.5.
Howard: 42:44
Yeah, and postpartum hemoglobin of 10.1 or something yeah, I get those all the time. I’ve even seen patients sent to the emergency department direct from the WIC office because a point of care capillary hematocrit was abnormal. This, I think, is related to how the WIC program is funded, and I believe their funding is based upon documenting and showing that pregnant patients are anemic and that this anemia is due to iron deficiency, because then that validates the idea that it’s due to a nutritional deficiency and therefore we need to improve nutrition and need federal funding to do that. But you know, if that’s the case, the funding laws from Congress just maybe changed not to be based on a metric that doesn’t actually promote well-being during pregnancy. We can supplement women and children and infants through the WIC program without linking it to a metric.
Howard: 43:29
That’s irrelevant, and I think there should be a broader conversation about changing our labs to reflect that the patient is pregnant, why it amazes me that this hasn’t happened. Why don’t we have a complete blood count and a comprehensive metabolic panel, for that matter, or other labs that reflect the normal ranges for a pregnant population? This is so easy to do in the age of electronic health records and this affects a lot more than hemoglobin, for example, a normal appearing creatinine based upon that 200 pound white male metric may actually reflect acute kidney injury for a pregnant person, whereas what might look like a low creatinine is, frankly, just normal for her. We’ve all learned to live with this, but outside of the OB-GYN community, like in emergency rooms, for example, or primary care offices, this information isn’t always readily appreciated and it leads sometimes to missed or over-diagnosis.
Antonia: 44:22
Yeah, there’s a lot of other labs in the same situation. I’m thinking of LDH or alkaline phosphatase, for example.
Howard: 44:31
Yeah Well, I don’t know how much this guideline will practically change what many of us are doing, but I do think that there’s probably too much iron supplementation occurring during pregnancy without a good, evidence-based reason.
Antonia: 44:43
Yeah, and there are potential problems with iron overload. We discussed before about the possible link to increased rates of preeclampsia with iron overload, but they do acknowledge that there are at least lots of side effects related to iron supplementation, and it would be nice not to make some of the unpleasantries of pregnancy worse by universally giving iron for no reason. Well, okay, we have a little bit more time left to do our historical segment, so I think you were going to discuss the history of antenatal steroids and how they came to be used to treat and prevent complications of prematurity.
Howard: 45:22
So, yeah, one of the sad things really about obstetrics is that we have almost nothing that we can do to prevent or treat preterm labor. We’ve talked about a lot of different things and a lot of things that are used, but if you’re a frequent listener to the podcast, you know that we really don’t have evidence-based ways of stopping labor outside of cerclages perhaps for a few well-selected patients. We really don’t have evidence-based ways of stopping labor outside of cerclages perhaps for a few well-selected patients. We really don’t have any way to prevent preterm labor and preterm delivery. More importantly so, the huge difference in outcomes that we’ve seen in infants born prematurely today, compared to 10, 20, 50 years ago, is due largely to the administration of antenatal corticosteroids and then, of course, parallel to that, huge advancements that we’ve made in our NICU technologies and the care for these smallest newborns.
Antonia: 46:14
I remember when I was a med student, going through my rotation, you would tell us that corticosteroids reduce the risk of all the three-letter acronyms that we learn about in NICU. So RDS, ivh, nec, rop, pda.
Howard: 46:33
Yeah, a good test-taking memorization strategy. But yeah, and to not alienate our audience too much, those are respiratory distress syndrome, interventricular hemorrhage, necrotizing enterocolitis, retinopathy, prematurity, patent ductus arteriosus and other things like the lower risks of cerebral palsy and visual and hearing impairments, learning disabilities, behavioral issues. Steroids are the single greatest advance that we have in terms of our management of preterm labor that we’ve ever had, and for the time being, it’s all we really do that’s meaningful, other than antibiotics and making sure they’re delivering in the right place for the NICUs there.
Antonia: 47:09
Okay, well, give us a quick history lesson of how we got the steroids.
Howard: 47:13
Well, the beneficial effect of corticosteroids is another one of those serendipitous discoveries that went on to change history. So many of the really important medical discoveries and otherwise in life were not intentional but were by chance. Penicillin, for example, comes to mind. But in the late 1960s a New Zealand researcher named Graham Liggins was trying to understand what caused the birth reflex in sheep, in other words what caused sheep to go into labor, and he suspected that there was a steroid hormone that might initiate labor, something given by the offspring to the or the placenta or something like that that would initiate labor. So he used the sheep model and he used large doses of steroids to try to induce labor. And when he did he observed that the lambs that were born who had been exposed to steroids had more mature lungs and much better survivability at a lower gestational age, with fewer respiratory problems, compared to the ones who hadn’t been exposed.
Antonia: 48:13
So he was in New Zealand. So was he a Kiwi.
Howard: 48:17
I think that’s what they’re called. That’s the vacuum.
Antonia: 48:19
Well, hopefully that’s not like a derogatory term. That’s not how I’m meaning it.
Howard: 48:23
Let us know if Kiwi is the good term or the bad term we should go visit and find out in person, anyway. So he started working with a pediatrician after he figured this out, named Ross Howey.
Antonia: 48:34
Oh, that’s, your name.
Howard: 48:36
Don’t go there.
Antonia: 48:36
Okay, Howey, I will not go there.
Howard: 48:39
All right, auntie. No-transcript. Subsequent studies.
Antonia: 49:07
That’s pretty good, so I would assume everyone just started giving these steroids immediately, right? No Okay?
Howard: 49:16
Never happens that way right. Even for something this beneficial, it still seems to be the norm that it takes about 17 years for an evidence-based practice to become common. So folks were worried about potential negative effects of giving these steroids, and most obstetricians in fact did not adopt this into their practice routinely. Finally, in 1994, so that’s nearly 20 years after some of the confirmatory studies there was an NIH consensus conference that looked at a meta-analysis of what then was 15 randomized controlled trials, and they concluded that antenatal corticosteroids should be administered routinely from 24 to 34 weeks of pregnancy for pregnancies that were at risk of preterm delivery. It still took a lot of work after that to make this become almost universal.
Antonia: 50:04
Okay. So even right now there’s still a lot of unanswered questions. So what’s the very earliest gestational age where there might be a benefit, because we know in some cases it’s possible to resuscitate before 24 weeks. And then what? Also, what’s the latest gestational age where there might be a potential benefit, like we’ve been doing the late preterm steroids and we’ve talked about that before. And what’s the role of the rescue or the booster doses and how beneficial is any of it in a day and age where we have CuroSurf that can be administered to the newborns after birth, because we’ve fallen into a practice pattern of giving steroids really to any pregnancy that could deliver between 22 to 37 weeks, but the evidence, especially for those later weeks in particular, is almost non-existent.
Howard: 50:55
Yeah, it reminds me of the hype cycle where we may be currently with steroids and what’s called the irrational exuberance phase and, as we discussed earlier this year, there was a new study that really showed no benefit at all in administering the steroids after 34 weeks, and that might be the start of bringing us back to a more rational and evidence-based practice pattern. We’ll see. But when you find something as useful as this, well, it’s natural to want to use it in an expanded group of patients who might see benefit from it, and that’s what happens during the irrational exuberance phase of the hype cycle.
Antonia: 51:30
Can you review the hype cycle quickly for the audience?
Howard: 51:33
Sure, I did write a Howardism about this a few years ago and can put a link to that, but basically this is something that comes out of the tech industry and explains how hot new products or new technology or whatever are adopted into the marketplace. So after the initial innovation, there is a period of slow adoption and for corticosteroids that was the first, really 20 years or so after the initial publications. Then there’s this period of irrational exuberance and we might be in that period now where we’re just trying to use it on more and more patients, any population who might benefit from it. If they’re like the population that we prove benefit from, they’re the next population over the next week, over whatever, maybe we should use it on those patients too.
Howard: 52:16
And then usually what happens is we reach a peak of overuse and we have all these inflated expectations that this is such an amazing thing. And then there’s this negative recoil from that overuse. We start to see patients harmed by it. Potentially Maybe there’s there is hypoglycemia in those later pregnancies, things like that and didn’t have the outcome we thought it would, didn’t make a difference. And so we find over time that our inflated expectations were wrong. So we become a little disillusioned with it.
Howard: 52:44
So, for example, the paper previously that she mentioned showed that use after 34 weeks wasn’t beneficial. Maybe that’s the beginning of that snapback. Unfortunately, usually this leads then to a period of profound disillusionment and then a trough of underutilization, as we just assume. Well, it’s not as good as we thought it was, it’s not good for much of anybody. And then eventually, hopefully, we enter into a phase of what’s called the slope of enlightenment, where we put all the evidence together, the good and the bad, and find the rate of appropriate utilization for whatever that might be. And I would predict that for this, appropriate utilization in the future might look something like limiting the steroid use to 23 to 34 weeks perhaps, and in probably not doing booster shots, except in maybe rare situations, something like that. So the literature matures, more studies come out and over time we negotiate these things back, hopefully, to a rational place.
Antonia: 53:50
Well, hopefully, if we know about this hype cycle, we can predict it and just skip the unnecessary underutilization phase or really just skip past the overutilization that we’re in too.
Howard: 53:57
Yeah, but it never really happens that way, partly because some of the hype and this is true in the technology world, the hype is promoted by people or companies or whoever who have money to make or notoriety to gain or fame or academic promotion or whatever. They want to believe that this new discovery and this new thing is the best thing ever. And so, in the article that I’ll put a link to, I discuss this in the context of hormones, where, when these hormones first came out, we didn’t know what to do with them, what they were good for meaning like estrogen and the ability to have purified estrogen that we could give to human patients and produce and things like that but the companies really wanted to sell it. And then we made over promises that companies did that weren’t science-based, that it was going to make you live forever and it was the fountain of youth and women would have no heart attacks if they took it. It was preventing heart disease and all that.
Howard: 54:51
And so at one point, Premarin and Prempro were the number one and number two bestselling drugs in America, not based upon studies that said that all these women should be taking it and that it had all these benefits, but based upon that was where it was in the hype cycle, and then we had the Women’s Health Initiative trial and then we entered into this period of disillusionment where we’ve just lived through this, where folks were scared to use it.
Howard: 55:18
And I saw a patient recently who had a hysterectomy with her ovaries out at a relatively young age about 30 years ago, and she’s in her 60s now and then she was put on estrogen afterwards and then a few years into that she was told by her doctor, after the WHI came out, that estrogen basically caused heart disease Not that it didn’t prevent heart disease, but that it caused heart disease and breast cancer and she shouldn’t take it.
Howard: 55:46
So she, like a lot of women, stopped taking it around 2002 and 2003. And now she has profound osteoporosis. And so we are in a slope of disillusionment and underutilization, probably right now, and actually we have a couple of studies coming up in the next episode or two that highlight the underutilization of hormones in women, and so we’ve not yet reached that slope of enlightenment. Perhaps but this happens all the time and look for it you may be caught up in your own hype cycle right now about something that you’re using, or think Da Vinci, or think V notes or think something like that, where we’re kind of using it with irrational exuberance.
Antonia: 56:28
Some food for thought there. Well, we should wrap up for today. So the Thinking About OBGYN website will have links to things we talked about and remember to tell us about apps that we forgot to mention on the Instagram page, and we’ll be back in a couple weeks.
Announcer: 56:49
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