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 9.8 Rethinking Bacterial Vaginosis and More!
In this episode, Antonia and Howard explore the groundbreaking study on treating male partners for bacterial vaginosis, revealing significantly reduced recurrence rates and challenging our traditional understanding of BV pathophysiology.
Plus:
• Evidence doesn't support treating mild gestational hypertension with antihypertensives
• Studies confirm acetaminophen in pregnancy doesn't cause ADHD or autism
• New research questions the benefit of routine postpartum thromboprophylaxis
• The history of heparin and coumadin
00:00:34 Treating Mild Hypertension in Pregnancy
00:06:14 Distinguishing Chronic vs. Gestational Hypertension
00:15:46 Male Partner Treatment for Recurring BV
00:27:09 Understanding Bacterial Vaginosis Pathophysiology
00:35:42 Ineffective Treatments and Alternative Approaches
00:53:04 Tylenol in Pregnancy: Debunking ADHD Claims
00:58:02 Postpartum Thromboprophylaxis: Evidence Against Overuse
Follow us on Instagram @thinkingaboutobgyn.
Welcome to Thinking About OB-GYN. Today's episode features Antonia Roberts and Howard Harrell discussing bacterial vaginosis treatment and much more.
Speaker 2:Howard.
Speaker 3:Antonia.
Speaker 2:What are we thinking about on today's episode?
Speaker 3:We've got a few different things to talk about, including we're going to spend a bit of time on this new article about male partner treatment for bacterial vaginosis, or at least recurrent BV, and a couple of other new updates. But first, what's the thing we do without evidence?
Speaker 2:How about giving antihypertensives for gestational hypertension or even preeclampsia without severe range blood pressures? This is something I've definitely done in the past, especially in cases where it wasn't totally clear whether we were dealing with chronic versus new onset hypertension in pregnancy.
Speaker 3:Yeah, sure. So typically we think of treating blood pressures for maternal benefit whenever the systolic pressure is above 160 millimeters of mercury and or the diastolic blood pressure is above 110. And this is for maternal benefit, to prevent myocardial infarction, congestive heart failure, renal failure, stroke, things like that in the mother. But we might diagnose gestational hypertension or preeclampsia without severe features, without severe blood pressures, in patients who have blood pressure is lower than that, above 140 over 90, but something less than 160 over 110. And in that range the maternal benefit is very minimal to maybe nothing over a short few weeks or months for treating those mildly elevated blood pressures, that short-term treatment. And there might be negative fetal implications, especially in a context where you're dealing with a placenta in, say, a gestational hypertensive or preeclamptic patient that's already sick in terms of under-perfusing the pregnancy, because that may be one of the reasons why the blood pressure is elevating is to help perfuse the fetus better. Then we drop that mean arterial pressure down and circumvent that.
Speaker 2:Yeah, and I think there can be a theoretical argument at least for either side treating or not treating these mild cases. So, theoretically again, treating someone who has new pressures 140 over 90 or higher could potentially lower the risk of developing those more severe range blood pressures and their associated complications like having a stroke or something like that. Theoretically at least, treating could lower the risk of developing the severe range blood pressures and then their associated complications for the mother, which could include things like a stroke, for example. But I think this idea has been extrapolated from the CHAP trial, which focused on mild chronically hypertensive patients in pregnancy, and from that trial we saw that treating those patients tended to prolong the pregnancy without harming mother or baby. But, as you like to remind us, almost every episode it's not about having the superior theory, it's really about the evidence. So what does that tell us here?
Speaker 3:Yeah, but also maybe the confusion stems from the fact that that trial focused on patients with chronic hypertension. So I think in this context, we're talking about new onset hypertension, gestational or, say, preeclampsia without severe features, which probably has a different, does have a different pathophysiology than chronic hypertension. So prior to 2022, prior to that trial you mentioned, we wouldn't treat mild blood pressure elevations in patients who had chronic hypertension while they were pregnant. In fact, we might take them off of the medicine and see if they had severe range pressures or not, and leave them off of it if they didn't. That had nothing to do, though, with gestational hypertension or preeclampsia without severe features, but then the landmark trial that you mentioned showed that it was safe to treat those mild blood pressures throughout pregnancy, and, though it didn't necessarily improve fetal outcomes, it certainly didn't worsen them, which had been the concern before that we would underperfuse the placenta. And they also found that it led to fewer diagnoses of preeclampsia, for whatever that's worth, although I think that that's really a byproduct of how we diagnose it.
Speaker 3:Diagnosing superimposed preeclampsia or chronic hypertension is difficult. If you see better controlled pressures, you're probably less likely to do that. So, in other words, it probably weeded out some of the marginal calls or over-diagnosis or false diagnosis of superimposed preeclampsia without actually impacting the true rate of preeclampsia. Always remember that the rate of diagnosis and the rate of disease are not the same thing. But the point is, our long-held concern that there would be more fetal growth restriction or other issues associated with chronic uteroplacental insufficiency turned out not to be true, at least in that study. So we started treating patients with chronic hypertension who had mild blood pressures, whereas before we'd only treat those with severe pressures and basically tried to keep the mildly hypertensive patients in the normal range.
Speaker 2:Yeah, and it's, I think, still very easy to conflate chronic versus gestational hypertension.
Speaker 2:After all, one is a risk factor for the other one, so it seems like there's quite a bit of overlap there. But there are still some key differences in the pathophysiology and management and I think there's just been this spillover effect where people have gotten into the habit of treating mild hypertension in pregnancy and assume that that applies universally to all cases of hypertension in pregnancy. But as a brief reminder, gestational hypertension is diagnosed by new onset hypertension after 20 weeks of pregnancy new onset hypertension after 20 weeks of pregnancy and it's a good practice whenever we're diagnosing that, to make sure that we really have excluded any even potentially undiagnosed underlying chronic hypertension, if possible, like done maybe a good medical history, even family history, blood pressure review, if there's any prior encounters we could look back at, etc. Just so that that doesn't become a question later on. And then we decide oh, we thought you were gestational, but it turns out you probably really were a chronic hypertensive. So either there is chronic hypertension that predates pregnancy or there is not, and then we diagnose it after 20 weeks.
Speaker 3:Right and it could make a difference in management at the end.
Speaker 3:But I think that there's a lot of cases where it may be unclear. I can imagine a patient who might have risk factors for hypertension but she never had a diagnosis. She shows up at a 22-week visit for the first time with an elevated blood pressure and then you see that confirmed on a later visit. And in that case you might rightfully assume that she had undiagnosed chronic hypertension, particularly if she'd had minimal care prior to pregnancy. Maybe she hadn't been to a doctor in five years before she came to the doctor for the first time when she was pregnant. And remember that your blood pressure may tend to be a little bit lower in the first trimester and into the second trimester due to progesterone's effects on the blood vessels, and it's just a normal physiologic change, essentially up until about 24 weeks, for the blood pressure to be a little lower. So it makes sense that a person who, at 22 or 23 weeks now has a blood pressure of, say, 142 over 91, 143 over 90, maybe she has chronic hypertension rather than gestational hypertension.
Speaker 2:Yeah, and that would be more likely than the alternative, which is that she really wasn't hypertensive and now she has early onset preeclampsia, although that too is possible and it is something to consider carefully. But if you have reasonably excluded that this is preeclampsia or on that spectrum let's say she's asymptomatic, she has labs that are reassuring, maybe ultrasound that's reassuring, and any history that you're able to obtain really is highly suggestive of an underlying chronic hypertension, then you certainly should consider adding antihypertensives, as we do now because of the CHOP trial. But we do have to draw a line in the sand somewhere and if there is such marginal, if any true benefit of adding the blood pressure meds to those chronic hypertensive cases you can avoid more false diagnoses of superimposed preeclampsia and maybe gain a week or two of pregnancy for sure then we really need to be cautious about trying to extrapolate that to something that has a really different pathophysiology that would be preeclampsia, because the risks of underdiagnosing that or precipitating maybe some kind of placental insufficiency it really is not something to be taken lightly. And remember they were not included in that CHAP trial.
Speaker 2:So of course still you may be preventing a morbidity related to severe hypertension. That's still a good thing. But these patients are also known to have more labile blood pressures than a chronic hypertensive, and their progression to preeclampsia and severe preeclampsia is pretty unpredictable. So you could end up basically avoiding the spikes of high at the cost of having more lows for someone with labile blood pressures, and it could lead you to pushing their pregnancies longer than you otherwise would and maybe increasing the risk of some other acute event, like a seizure or liver capsule rupture, for example. And we don't know what the effect is on placental perfusion in preeclamptics. We just don't have the evidence to say that it would or wouldn't be affected. So if we're really confident that we're dealing with gestational hypertension or preeclampsia and this is not a chronic issue, then we really need to treat it accordingly.
Speaker 3:Yeah, and if you really believe it's chronic hypertension you've looked at everything and that's your suspicion then document it as that and treat it as that and do the extra kind of precaution to make sure you're not wrong. But that's okay. But, as you said, those marginal patients, the patients who didn't clearly have a diagnosis of chronic hypertension, were not included in the CHAP trial. So you're probably also talking about a milder patient anyway, and so don't pretend that that's going to be a population that's going to benefit from the treatment even as marginally as those in the CHAP trial did. So I've definitely seen no new hypertension diagnosed at 33 or 34 weeks in the mild range and have seen those patients started on antihypertensives. There was no doubt that this was new hypertension, with the goal of getting to 37 weeks and inducing them, and it was labeled in the chart as gestational hypertension or even PIH pregnancy induced hypertension a term that we, of course, no longer use, but it's still relatively prevalent, unfortunately.
Speaker 2:What don't you like about PIH? Does it not roll off the tongue?
Speaker 3:I'm not a big fan of how we so often seemingly change the names of things just to change them or for no great reason, like intrauterine growth restriction becomes fetal growth restriction or chorioamnionitis becomes intraamniotic infection, like some of these seem like they're differences without a distinction, and I'll make that argument for things like that that are just change for change's sake. But we haven't used the term pregnancy-induced hypertension in the literature since 1999 or 2000. The diagnostic criteria, classifications of hypertensive disorders in pregnancy underwent a huge change in 2000. So the whole paradigm that we practice under today, which has evolved a little bit, though it started in 2000.
Speaker 3:And prior to that pregnancy-induced hypertension and preeclampsia were thought of as the same thing. So that's the important distinction is we're not making a difference there with gestational versus preeclampsia. So going forward from the new classification, gestational hypertension and preeclampsia were different conditions with different diagnostic criteria. So in a proper sense, gestational hypertension and PIH are not the same thing, because PIH is essentially preeclampsia the way it was used prior to 2000. So when we say gestational hypertension, we're meaning something distinctly different from preeclampsia, and so we shouldn't use PIH anymore because in this case it's ambiguous and we stopped using it because we forked the road and gave more granularity, and so it's unclear when you say PIH, what do you mean? Do you mean gestational or do you mean preeclampsia? And we have different diagnostic criteria now.
Speaker 2:Okay, that makes sense. That reminds me a little bit of when we talked before about how gestational diabetes used to be called pregnancy-induced glucose intolerance. Oh yeah and of course the acronym for that is p-i-g-i don't say it, oh lord well, and I mean you can. Everyone knows what that sounds like, so yeah, so, and that change happened way before the terminology changed from PIH to the gestational versus preeclampsia, and so changing to gestational diabetes also created a more unified naming structure. That gave maybe more specificity when you're talking about GDMA1 or 2, for example.
Speaker 3:Right. Yeah, there's some parallelism there Pregnancy-induced glucose intolerance, pregnancy-induced hypertension, but now it's gestational diabetes, gestational hypertension. So it's nice to be consistent in that sense. But yeah, the abbreviation PIGI written on charts is just no bueno for describing gestational diabetes. Anyway, we don't treat new onset mild hypertension diagnosis after 20 weeks. That's not the current recommendation. We do treat severe range blood pressures for maternal benefit. You could argue for fetal benefit if we had evidence that it prevented abruption and it might on the margin in those severe pressures. But mild doesn't, and so most of those pregnancies that are treated with medicine because they have a severe feature are going to be delivered at 34 weeks unless they become unstable and have to be delivered sooner. So we essentially shouldn't be seeing that 34 to 37 week people on medicine anyway. Or you're arguing they should have already been treated and you might mask higher blood pressures that would indicate delivery at 35 weeks because you put them on medicines for what were mild pressures but now you're masking the severe pressures.
Speaker 2:We probably could do a whole segment, if not a whole episode, on outdated terms for things in OBGYN and that could generate some fun reader listener mail. I want to hear if anyone has reactions to the thought of calling diabetic pregnant women piggy. Yeah.
Speaker 3:Well, that sounds like a good fun podcast episode. I'll start keeping a list when I hear these things, but Okay, sounds good.
Speaker 2:Well, let's move on. There's a newer article in March 6th 2025 New England Journal of Medicine that made a big splash in all the little medical headlines that I've seen. So it compared male partner treatment versus no male partner treatment to prevent recurrent bacterial vaginosis in women. So, in other words, women were assigned to either receive traditional therapy, where they alone, as the patients, were the ones treated, or the other group was assigned to receive that treatment along with their male partners also being treated, and the difference in recurrence rates was so significant that the IRB actually ended the study early because they felt that the traditional arm, with only women, not their partners, being treated, was being harmed by continuing the study.
Speaker 3:Yeah, this could be a big change. So this is something that folks have talked about for years, this idea of partner treatment. There's an accompanying editorial in that edition that tells us that 60% of patients will have recurrence within a year of treatment for BV. The various bacteria involved in bacterial vaginosis, of course, can be transmitted from person to person, but we've so long had the belief and the thought process that this is a pH imbalance of the vagina rather than a sexually transmitted infection, that only in the rarest cases have we focused on it as being something that might require partner treatment, even though it is a bacteria.
Speaker 2:We already recommend treating both partners. For other things, like if we detect mycoplasma genitalium on the female, we consider that more of a classic sexually transmitted infection, similarly to chlamydia, for example, and people don't think of mycoplasma as something that could just originate in the environment or the gut or normal microbiome, as they often do for Gardnerella Prevotella. Those things that are under bacterial vaginosis and mycoplasma chlamydia require different antibiotics than BV does, so that's maybe another way people categorize them differently, but it seems like there's a little bit more overlap than we've traditionally thought.
Speaker 3:Right, and men can also have symptoms, though, from mycoplasma genitalia and obviously chlamydia and some of these other things that we consider classic STIs. But traditionally we've thought of bacterial vaginosis as something that can occur without sexual activity and we don't recognize a clinical symptom course in men. And also we should point out that there have been previous trials done that looked at partner treatment prior to this one that didn't show benefit in treating the male partners for bacterial vaginosis.
Speaker 2:Well, in this study in the New England Journal at the 12-week point, only 35% of the group that had partner treatment had recurrence, compared to 63% in the control group had recurrence compared to 63% in the control group and that 63% matches the typical one-year recurrence rate that we have historically seen reported. Now authors here say the difference is that, compared to prior studies that didn't show benefit from partner treatment, here they used both oral and topical treatment for the men, and previous studies have benefit from partner treatment. Here they used both oral and topical treatment for the men and previous studies have just used oral treatment. So in this one the men got oral metronidazole and topical clindamycin.
Speaker 3:Right, and the other huge difference is that 80% of the men in this study were not circumcised. So this is a trial that was conducted in Australia, where circumcision just isn't done that often. People should go back and listen to our circumcision episode. It might be the most popular one ever, but we picked up some non-OBGYN listeners on that one. But it's certainly possible this could play out differently if the study were done in a population of circumcised men, and 87% of the women enrolled had previous bacterial vaginosis infections as well, so they're really focusing on recurrent disease. They also only included women who were in monogamous relationships.
Speaker 2:It would have been interesting to see breakdown rates among outcomes for the patients whose partners were versus were not circumcised, and they didn't break that down here. Unfortunately, there are some other studies already out there that suggest BV in women is up to 40% less common if they have a circumcised partner compared to uncircumcised, although some other studies then will find no difference or no association. So I don't know yet if I would go so far as to say to my patients with recurrent BV tell your man to go get circumcised if he isn't already, or that I would tell my pregnant patients that are expecting a little boy that you should get your boy circumcised for this reason.
Speaker 3:Yeah well, and this particular study was probably underpowered to have any power from comparing the circ to uncirc to men. So I'm sure someone will do this study going forward and circumcise men as well. But the folks should go back and listen to our circumcision episode if they are thoughtful about this, and the pro-circumcision people might argue that this is a benefit of male circumcision. Although, again, do you cut off an organ because it can become infected, when that infection can be treated with a simple antibiotic?
Speaker 2:Right, yeah. So just to hearken back to that episode, like it's still, circumcision still is not a universal recommendation. It's not that. It's one of those things that is so clearly established that we just tell people they really should do it. It's not necessarily like we do for many other things, like vitamin K after birth or all the vaccines we do, and I know there's still so much controversy about a lot of those things. But yeah, for circumcisions, I'm still at least emphasizing to people that this is completely elective. You don't have to do it. There's really what's the risk or benefit? It's questionable.
Speaker 3:Yeah, and I do think that the applicability of this study to couples where the partner is circumcised continues to be the major weakness of how we implement this. So hopefully in the future we'll have some clear information about the balances of risks and benefits for circumcision or for treatment of circumcised men in our population. We do have lots of data about the pros and cons of circumcision. Again, people can go back and listen to that, but is this a reason to get circumcised because it harbors these organisms? I do think we have all the information we need to counsel patients about circumcision, the pros and cons, and be able to let them make their choice and I think that's what people would conclude if they listen to that episode is that it's an elective, culturally based procedure and they don't do it in Australia that commonly. So this was an uncircumcised population.
Speaker 2:So in season six, episode nine is where we really just spent almost the whole time, I think, talking about circumcision and all of this stuff. So go back and listen to that if you haven't already, and now that we're again having some circumcision considerations with this new study, it might be a good refresher. So yeah, I'm still open to new evidence about benefits or risks about circumcision. Of course there can be some benefit, it sounds like, at least for some boys and their future partners. So we'll keep circling back whenever it comes up again.
Speaker 3:Well, so on that note, then, getting back to the paper, this new paper, the fact that they found any benefit at all from partner treatment does show that we should think of bacterial vaginosis more like a sex transmitted infection rather than a change in your vaginal pH. The lack of such a benefit in previous trials is why we've not yet thought of this really at least the broader community as a sexually transmitted infection in the past. But again, these, in fairness, were very small trials and they may have used an ineffective treatment regimen when you understand the organisms here. So there is some concordance in the microbiota of sexual partners and the male partners, and they tend to harbor these organisms in the distal urethra and in the subprepucial space.
Speaker 2:The what space yeah.
Speaker 3:So I don't know that I've ever said these words before as an OBGYN the subprepucial space. So the prepus is a fancier word for foreskin Surely it's not pronounced prepus, but I think it's prepus. But you need to have a foreskin to have this space. And so, again, it'll be interesting to see if the data from this trial is replicated in a similar trial with mostly circumcised men. But there is a little microbiome in this subprepucial space, but there is a little microbiome in this subproputial space and it's shared with the distal urethra and so, even if you are circumcised, you still have those organisms in the distal urethra just a lower count of them, and the bacteria that live there tend to match up with the female sexual partner. If you look at both of them, they share a common microbiome. Look at both of them, they share a common microbiome. It's also been shown that bacterial vaginosis, as a new infection, has a characteristic incubation period following sex with a new partner. So just like herpes or gonorrhea or chlamydia or any other STD.
Speaker 2:But we know that women who have not been sexually active can just as well get vaginitis, and presumably that includes bacterial vaginosis as well. Right, or are we understanding that completely wrong?
Speaker 3:Yeah, this is really interesting, so I'll put a link to an article from 2019 that proposes an updated conceptual model for the pathogenesis of bacterial vaginosis, and this is from the Journal of Infectious Diseases. We still have a lot of controversies about this topic. When you get into the literature, it's fascinating. We take everything in life that's very complicated and we make it into a black and white thing and at the end of the day, most providers are out there with a very simple approach to diagnosing and treating BV and it really just doesn't do justice to the complexity of all the controversies here.
Speaker 3:There's a controversy about whether or not BV is due to a single organism, if ever, specifically Gardnerella vaginalis, which is present in about 95 to 100% of cases of BV, or whether it's polymicrobial, and then which microbiota are involved in that. They also discuss whether there are different types of Gardnerella, including some that are normal flora and others which maybe are more pathologic. It's true that Gardnerella is found in virginal women, and it's also found, obviously, in women who don't have a clinical diagnosis of bacterial vaginosis based upon Amsel's criteria or the Nugent score. So this obviously creates a problem with the molecular tests that they just test for the presence of Gardnerella and we discussed before that. Bv is still a clinical diagnosis based upon criteria, usually Amsel criteria. It's not defined by a test that looks for Gardnerella. Having Gardnerella in your vagina does not equal the diagnosis of BV, although clinical practice seems like it's going that way, as people don't actually do AMSL criteria in their office. But that molecular test doesn't supersede the criteria.
Speaker 2:Yeah, so if a patient has classic symptoms of BV, classic exam findings, but the test does not show Gardnerella, that also doesn't exclude BV.
Speaker 3:That's right.
Speaker 2:There's a good handful at least of other organisms that could cause the same clinical criteria and symptoms, and these days, at least from what I'm seeing and what I have available, most molecular tests are already checking for a panel of bacteria, not just Gardnerella.
Speaker 3:Yeah, and they may be, but then that creates its own problem too, where the same issue to those other organisms are they singularly causes or whatever? So none of those tests, and they just may be adding cost to the patient by testing when all they really needed was a pH test and a wet mount. So a lot of companies are marketing those, but again, none of those organisms replace the clinical criteria.
Speaker 2:Okay. Well, that article from 2019 talks about four different subgroups of Gardnerella that each have distinct properties, and they talk about how patients with more than one type are more likely to have signs and symptoms of BV, whereas patients who only have one of the four different types tend not to have any vaginitis symptoms. So it could be, then, that healthy women have one of those four particular types of Gardnerella and this is almost certainly a normal flora for them, but then if they are also exposed to a different subgroup, let's say from a partner, then it becomes a pathologic scenario where they get irritation and symptoms, and in the article they also suggest that co-infection with other complete other type of organisms, especially Prevotella bivia or hopefully I pronounced it right the Atopobium vaginae, may also lead to the symptoms of BVE, more frequently so than if it was just that organism alone. But when they have Gardnerella and one of those others, they're more likely to seek care for it, and obviously those other organisms might be sexually transmitted as well.
Speaker 3:That's right, yeah, so they propose that sexual transmission of some more virulent strains of Gardnerella, or just maybe different strains, displaces the normal vaginal lactobacilli and then a biofilm starts to develop in the vagina and as the number of virulent strains of Gardnerella increase and there's a synergy that may form with other bacteria like the Prevotella strains you mentioned, and then all of these BV-associated bacteria produce an enzyme called sialidase which breaks down the mucin layer of the vaginal epithelium.
Speaker 3:This allows increased adherence of other BV-associated bacteria to the vaginal epithelium, including the atypobium vaginae, and likely causes more symptoms of burning and inflammation and discharge. The atypobium is important here because it tends to be resistant to metronidazole but susceptible to clindamycin. So this could be a key as to why the men needed to use both, because when they were given just metronidazole in other studies, well they may not have been eradicating the atobobium vagini species. So co-treatment with both antibiotics, as they did in this study, might be the key, because recurrence of BV is probably linked to receiving either some of the more problematic types of Gardnerella or the synergy between other bacteria like the atopobium, and just treating with one antibiotic didn't get both.
Speaker 2:The atopobium can be found in as many as 80% of women who are diagnosed with BV and we think is related to a lot of the treatment failures and recurrent cases. So in the same way, adding clindamycin just to the female patients you're already typically giving them metronidazole, but then if you also add clindamycin, especially when you have recurrent BV or treatment failure, is probably a key to actually resolving their symptoms. And also, this bacteria has also been called by a different name which is, I don't think, any easier to pronounce. It's Fanny Hesia Vaginae, in case anyone was interested. I don't know the backstory behind either of those names, so I don't know if maybe one of our listeners out there wants to do a deep dive and let us know. And you were just complaining about calling the same thing by different names for no good reason, so I don't know if there's a good reason here.
Speaker 3:I feel like some basic science researcher had their loans financed through Fannie Mae or something Like. I'm going to name this irritating antibiotic after a microbiome after. Fannie Mae Fannie.
Speaker 2:Hesia.
Speaker 3:I don't know.
Speaker 2:It's a good theory.
Speaker 3:It's probably someone's name. We're not. We respect that. It's probably the person who found it, yeah.
Speaker 2:Yeah, yeah, well, and either whichever one you want to call it, there have been rare reports of this causing more than just vaginitis actually bacteremia and osteomyelitis, even in males, pteremia and osteomyelitis, even in males, and it's been found in cases of fetal loss, where they did a culture of the tissue and found this. So the classic thinking that BV is just a minor annoyance, only related to vaginal pH, for example, no serious risks, and completely unrelated to sexual contact, has really been, I think, debunked here. And I'll repeat, just for emphasis, that this weirdly named one, atopo BM or Fandihasea, can resist the classic BV treatment of metronidazole.
Speaker 3:The idea that BV is a direct result of abnormal vaginal pH and that you have to fix the pH to fix the BV is really misguided, and a lot of therapies and alternative treatments for BV, or recurrent BV in particular, or things that are meant to prevent BV, are predicated on this misunderstanding about pH that we've promoted.
Speaker 2:Yeah, there really is quite an industry of over-the-counter and direct-to-consumer treatments for recurrent BV, including many different types of oral and vaginal probiotics as well as boric acid suppositories, and anyone that gets recurrent BV is really going to get fed up with it, and the longer it goes on, the more desperate they're going to be to make it go away and the more willing they will be to spend their own money on these treatments, especially when they've gotten metronidazole so many times from different doctors or other providers and it's just not working.
Speaker 2:And then maybe they're starting to think it's something else, like maybe this is myofascial pain, maybe you should go have pelvic floor PT or something. And the patients are just like they're starting to feel like this is a dead end here and they need to find their own treatments. And I'm betting that's probably how douching ever became a thing, because people see this on the aisles and grocery stores and they feel unclean, they feel like there's an odor and they just want to flush out everything. And hopefully by now most people know that douching only either worsens and maybe even creates these problems and is really never appropriate for any reason.
Speaker 3:Right. Importantly, these strategies that you see just are not evidence-based. Boric acid might have some activity against some pathogens that are resistant to bacteria, but it also is very irritating. I think a lot of patients who have sometimes been misdiagnosed with BV. They might have cytolytic vaginosis, which is an overgrowth of actual lactobacillus in the vagina at least that's how it's characterized. It probably is the case that boric acid is helpful for those patients, because you're just trying to kill the normal flora essentially, but it's a very irritating treatment and not something that people should be trying to use at home because they have BV. And as for probiotics, even if they are effective at reseeding lactobacillus into the vagina, which is definitely not the one thing you want to do if you have cytolytic vaginosis, that alone will not do anything about the pathologic bacteria that are present, and so, once again, there are no high quality trials that show that these treatments are effective, or as a treatment or a preventative, either by the oral or the vaginal route.
Speaker 2:Yeah, and with BV, another diagnostic criteria that's been described is having a lack of normal lactobacilli, and so with that in mind, you can definitely see where the theory of taking more lactobacilli supplements would come from, and there's a lot of lower quality studies that have conflicting results about this.
Speaker 2:So the best we can say with what we know right now is most people can take lactobacilli, probably with no harm, maybe with some benefit, maybe not, but then if they have cytolytic vaginosis, then they're definitely not helping themselves. And then the pH thing again, that's a whole nother thing. That's also part of this sort of confusion, I think, because abnormal pH is part of the diagnostic criteria for lots of different types of vaginitis, including BV. People would assume, maybe as an oversimplification, that fix the pH, then that'll just fix the vaginitis. I've found plenty of online guidelines, not from academic medical societies, but just different websites, about how to do baking soda baths as a treatment for, specifically for, cytolytic vaginosis which is weird because they also use acid for it yeah, we're going to use baking soda and we're going to use acid for the same thing, yeah so which is it right?
Speaker 2:but so I've thought about that, like maybe there's also the idea that just the baking soda itself can help soothe the sensation of irritation, rather than doing anything to the ph. But I also think that it might just be an easy placebo treatment, because people tend to have baking soda at home and it's a cure-all.
Speaker 2:Yeah, basically, and sometimes we do add bicarbonate into nerve blocks, like with pudendal nerve block anesthetics. It can ease the sting of the anesthetic. So maybe that's part of the theory here. But definitely, baking soda baths and anything else related to trying to influence the vaginal pH is purely based on expert opinion. It's not been studied in a controlled manner at all and I've seen different posts online. People have all kinds of different forums where they trade stories and stuff and people might do well for three days in a row of baking soda baths and then on the fourth day severe burning, worse pain than ever before. So I think right now I would look at baking soda and probably acid as well as just a totally anecdotal type of approach, not part of any evidence-based type care regimen for vaginitis.
Speaker 3:Yeah, and I don't know if I go so far as to say expert opinion maybe internet opinion but it really gives of progesterone for miscarriage or spinning babies for optimizing fetal position or all the stuff we talk about. It's anecdotal, it's not evidence-based, it's supposedly harmless because it's natural or it's something you can do at home without a doctor or something like that. But it may actually cause some unexpected adverse outcomes. I've definitely seen that with people using boric acid suppositories too much yeah, and maybe some people would say circumcisions fall under that oh wow, we need the little thing, the drum thing, the yeah yeah.
Speaker 3:Yeah, okay, well, and I'm not really sold on baking soda baths here, although I can see how someone might suggest that when they've tried all these things and a lot of it honestly may stem from misdiagnosis they just keep getting treated for something that doesn't work and what they really need is a better diagnostician and to get to the right treatment. But they try the baking soda. They don't really see overt inflammation. Your molecular swab doesn't show you know BV or something. Maybe there is excessive lactobacillus, if you have one that looks for that and you have this therapeutic imperative that you have to do something. And so then you tell your providers go and they Google this stuff. What do I do with the patient? With whatever? I don't think patients probably do realize that that happens.
Speaker 3:And so now you have doctors and mid-levels recommending boric acid or baking soda or things like that. But if you have a patient like that, I wonder if maybe they need to stop all those things. Stop the lactobacillus supplements, stop the acid that's killing everything, stop the baking soda that's changing their pH and making it more hospitable for the wrong bacteria and they're doing more harm than good. But it also could be the case that partner treatment might actually have some merit for these patients. And so here's an example of where an interventional trial has shown actual evidence of benefit from something we haven't been doing, versus a theoretic idea about altering the pH. So we should result on empiric evidence, not fanciful theories and complex ideas.
Speaker 3:And the pH thing also reminds me, like progesterone and miscarriage. Is the pH abnormal because you have the infection or do you have the infection because the pH is abnormal? In the same way, is your progesterone low because you're about to miscarry or are you about to miscarry because your progesterone is low? And it's the same mental problem. And so, just as the fix for miscarriage isn't adding progesterone, the fix for recurrent bacterial vaginosis isn't altering the pH of the vagina.
Speaker 2:Yeah, so we have a really good link here to the effect of the partner and the effect of treating the partner. This particular study did not look at same-sex partners, but there's no reason to believe that this wouldn't apply in those cases as well.
Speaker 3:Yeah, I agree that's disappointing. Hopefully that's another study that's done soon, but maybe even more so. Bv is more common among same-sex partners, and I imagine that's because the vagina is better able to harbor these pathogens than is the distal urethra or even the subprepuceal space of an uncircumcised man.
Speaker 2:There's that fun word again.
Speaker 3:Yeah, this is hopefully the last podcast we use it on, but yeah, okay.
Speaker 2:And the lead author of that 2019 article about the conceptual model for BV also wrote an editorial in the New England Journal of Medicine on these same points and acknowledges some of our limitations of our knowledge of this, and I still think there could be some pushback on the idea of classifying this as a sexually transmitted infection.
Speaker 3:Yeah, there definitely is. I had a conversation with this with a resident in DC a couple of days after it was published and immediately that was her instinct is that there would be harms of classifying this as an STI and certainly the intention isn't to make it feel like syphilis or something. But it will introduce new questions for patients and there's a potential, of course, for stigmatization of BV. If a monogamous couple suddenly has difficulty with a case of BV, does that imply infidelity? I think the difference here is that these bacteria are found in both male and female patients.
Speaker 3:Without symptoms, you can be in a normal state and in that sense might be considered normal flora. But each person tends to have a unique genital microbiota and maybe we should think of it as the clash of these microbiomes. Again, if you have any one of the subtypes of Gardnerella, then you're fine. So two people with two different subtypes now have sex and the female partner now has two competing or two different Gardnerella populations and then that's when the cascade starts and she may become symptomatic. So we don't want to imply to patients that BV is a sign of infidelity or something like that, or to stigmatize it in any way, but we also need to think of it in the right way, so we can treat patients effectively.
Speaker 2:Right and we know certain other things can be pretty hard to explain any other way. Let's say there's a new case of gonorrhea or chlamydia trichomonas, for example. But even in some other things we already consider STDs like herpes. They can be dormant for years and then crop up again and cause new infection in a monogamous couple that has remained monogamous. And similarly, hpv tends to linger and can get passed back and forth, even between the same partners over and over again.
Speaker 2:One clears it then just in time to basically be re-exposed and reinfected by their partner, been reinfected by their partner. So when, let's say, a married patient has a new case of HPV, whether it's condylomas or whether it's just an abnormal pap result, we never mean to imply to her that oh, your husband, he's been stepping out on you because of this. And I imagine it's possible that with BV, any change in the microbiome of a patient or their partner for any number of other reasons could trigger a new case of vaginitis that wouldn't have had anything to do with having new partners or multiple partners or undisclosed partners. So we probably need to think of BV more similarly to HPV, hsv and less like gonorrhea or trichomonas, and at the same time understanding that these pathogens are transmitted sexually will help us better treat the condition, to understand it.
Speaker 3:Agreed and do future studies that will benefit patients.
Speaker 2:So moving on a little bit. I assume you get email blasts from ACOG every day about new articles and headlines.
Speaker 3:Every business day.
Speaker 2:Yeah, and yeah, so do I, and sometimes I'm a little bit disappointed in the selections of headlines. Do pay a company that picks these things out for them and there's maybe not as much editorial oversight as there would be for the Green Journal, for example, but sometimes those selections are a bit frustrating. So, for example, on March 5, 2025, from the ACOG email blast, there was this headline maternal acetaminophen exposure may be associated with childhood adhd diagnosis in offspring. Study suggests and this is in reference to an article in nature, mental health, which, disappointing, they put it there, you as well. But this article provides no new clinical data but has some fairly bold claims saying, quote despite evidence linking prenatal acetaminophen exposure in adverse neurodevelopment in humans and animals, over half of pregnant women in most populations use acetaminophen. End quote.
Speaker 2:And you know that's already flawed on its face. But that's the gist of this article that ACOG wanted to link to us. So this is not a study that would tell us that there is a link between Tylenol use and autism or ADHD or any other neurologic disorders, and it adds no real evidence to this question. It's just repeating an unproven assertion in that sentence, and the frustrating part too, is that it's sent out in this email by ACOG to its members, so it gives a sort of implied legitimacy to it. And yet it was from a rather obscure journal that none of us otherwise would typically be reading.
Speaker 3:Yeah, but it's this article's picked up. It's picked up on the CNNs and the other newsfeeds at least it's in my newsfeeds. This sort of literature or this sort of articles get a lot of attention and they get clicks and people love to repeat them. And but yeah, there should be a certain amount of responsibility for which articles are promoted, at least by ACOG to its members, and which ones are not, which ones are just ignored. The medical and scientific literature is complex and full of all sorts of preliminary and speculative findings and unconfirmed or unrepeated data and, frankly, just bad papers that can be made to say or give the appearance of saying almost any conclusion you can dream of. So when you're curating those articles to share, there should be a responsibility to place such articles in context at least, or just to not give space to articles that don't deserve it. But I do have some good news for you.
Speaker 2:Well, finally, I'm ready for the good news.
Speaker 3:Well, there was an article and a review of the studies about the risk of ADHD and autism spectrum disorders in children exposed to acetaminophen in the Green Journal in February of 2025, and they concluded that there wasn't data to support any causal relationship and that we needed to make no change in our recommendations about using Tylenol during pregnancy. So basically, they found the opposite of what that ACOG email blast told us was true.
Speaker 2:Maybe I missed that headline in the February email blast.
Speaker 3:Or maybe it wasn't there, or maybe it wasn't there. Also, in February there was a review in the Journal of Critical Reviews in Toxicology is what it's called that looked at all of the preclinical science work about any potential associations and also they concluded that evidence was lacking to support any sort of causal relationship between acetaminophen and these conditions.
Speaker 2:I guess they forgot to add that too in their email blast.
Speaker 3:Perhaps We'll put links to them, but anyway, the consensus of current scientific evidence is that acetaminophen doesn't cause autism spectrum disorders and is not associated causally with ADHD.
Speaker 2:Well good, because that's not news. Autism has been around for way longer than acetaminophen has been around, or at least in widespread use, or even that childhood vaccines have been around, for that matter. And it has gone by a lot of other names in the past. Asperger syndrome was one of them. People called it Kanner syndrome just all these different names. People called it childhood schizophrenia.
Speaker 2:But there are very detailed historical descriptions of this still fairly mysterious condition that really predate any modern thing that people try blaming autism on. We've seen epidurals, microplastics, processed food, coloring, any of those things, and it's a little frustrating that we have to keep beating this dead horse and ruling out the same environmental causes over and over again in research studies. But at the same time it's encouraging that people still are putting in their scientific efforts, even if it's a little bit shouting into the void that like these don't cause autism. Stop targeting this stuff. And it is also encouraging that these negative studies are still getting put out into the literature and eventually, if enough people would accept that there's no single exposure, that if it was just eliminated, could 100% cut out all the cases of autism. Moving forward, then maybe more efforts could be focused on services and treatments and therapies for autism instead of trying to prevent it, which we still have not found a way to prevent it.
Speaker 3:On a completely unrelated note, did you know that RFK Jr and his law firm gets referral fees for patients who contact him and he refers them on to lawsuits over lawsuits over the things you just listed as relation to cancer and autism? That's what he does for a living.
Speaker 2:I'm not surprised, but I didn't know that.
Speaker 3:Yeah, so there are people making money off of this kind of fear tactic stuff out there and anyway, unrelated, not relevant to today's discourse, Okay. Well, another really important recent article that we should discuss is from the March 2025 Green Journal. There's a new study entitled Postpartum Pharmacologic Thromboprophylaxis and Venous Thromboembolism in a US cohort. They should limit the character count on those titles. This was a multi-center retrospective cohort study of patients who were given heparin-based pharmacological chemoprophylaxis postpartum and they looked at the rate of VTE within 12 weeks of delivery. So they included nearly 65,000 deliveries and in that group, nearly 14% of the patients in the group received chemoprophylaxis.
Speaker 2:Yeah, we discussed before about this, about how there's different criteria for people who should receive heparin or lovinox postpartum, and this study did not focus on those people that are in the higher risk that clearly undeniably should receive it. So, for example, people who have had a DVT before or have known high-risk thrombophilias. In this study these were the patients who fell under broader criteria that some institutions have and some don't. For example, they've had a cesarean or they have hypertension, or they have a BMI over a certain cutoff or age over a certain cutoff or things like that. And we also talked already before about a couple of studies that showed that more liberal criteria for anticoagulation resulted in no improvement in the number of DVTs compared to a more restrictive criteria, but maybe seemed to cause more cesarean wound complications. But right now we're still in a world where many institutions are still anticoagulating a significant percentage of their patients depending on criteria that they've homegrown and decided on internally.
Speaker 3:Right.
Speaker 3:In this new study they found that pharmacologic prophylaxis resulted in no difference in VTE risk compared to the patients who got no prophylaxis, but it did result in a higher rate of hospital readmission and wound complications, and their conclusion was that the current practice of administering thromboprophylaxis is ineffective. We discussed this, as you said, last year, I think, in 8.4, season eight, episode number four. The criticism, of course, will be that this was retrospective and not a prospective study, but with such a large sample size and with the propensity score analysis, that they did that honestly doesn't really matter. This very well may be the best study we have, the best piece of evidence we have. Compare this to a prospective trial with 1,000 or 1,500 patients. More importantly, I would point out to those who want to administer these medicines, which do carry significant risk to postpartum patients, that there is no prospective study or retrospective study that says that doing so is beneficial to the patient. So the burden is on the person wanting to give 14 or 15% of patients, as opposed to a couple percent, whatever that might be chemoprophylaxis.
Speaker 2:Yeah, so this is very emblematic of things that become the standard of care. And everyone starts doing it with great intentions because they want 0% PEs, but they do it before there's any good evidence of benefit. But once they've started doing it, it's hard to stop.
Speaker 3:Yeah, that inertial will again, but first do no harm. Of course I get the theoretic idea that certain patients are at obviously at increased risk of DVT and that we would like to prevent those DVTs. But you can't just ethically get away with using an intervention that all the studies so far say isn't working and potentially or does cause harm. It's a little harder when the intervention is relatively harmless. A little harder to make the case of not using is what I mean to say, which I think is where we're at now with. Like nifedipine is a tocolytic. We have no evidence that it's effective or beneficial to the fetus or the mother or improves any outcomes.
Speaker 3:But it's also hard to make an argument about, you know, stopping it. There's no great dangers that I can point to, that people are dying or something because they got a dose of nifedipine. So people keep using it as a tocolytic despite multiple randomized controlled trials now that say that it and all the other tocolytics are ineffective. And this also is probably where we're at with the whole 81 milligram of aspirin for prevention of preeclampsia. There just aren't any trials, which we've well documented on here, that say that it's effective at preventing preeclampsia and more and more studies seeming to come out every month or two. That agree with that. But it's also hard to argue that it does any danger, so that inertia favors continuing to use it. But in this case we not only lack any evidence that heparin or lovinox is effective at reducing the rates of DVT for patients with whatever combination of risk factors, but we actually see harm from it Higher readmissions, higher wound infections those are harms. Those are important harms.
Speaker 2:Yeah, and to put some numbers on that, 6.7% of patients receiving the anticoagulation were readmitted, compared to 1.7% of patients who did not receive it. But the patients who did receive it also were a group with more comorbidities. So the adjusted difference was about 1.36 percentage points. And for the rate of wound complications, again the adjusted difference was about 1.4, 1.5 percentage points.
Speaker 3:Yeah, so a small difference, but a difference, and ultimately for again, for folks who are interested in reducing the risk of thromboembolism in these at-risk patients, as we discussed, one of the most important things they could do is work on lowering their cesarean delivery rate in that population who's at increased risk for DVT and PE. Then also things like decreasing operative times and decreasing the amount of time patients spend in bed leading up to delivery, think bed rest for high-risk patients who might be hospitalized for a few days or weeks before they get delivered. But folks can revisit that episode 8.3, where we talk about the other literature about this topic. But this new study adds to the evidence that we should not be using anticoagulation for patients who don't meet the stricter criteria, the things like having a prior history of DVT or some of the known clotting disorders that we discussed in that episode.
Speaker 2:Okay, well, if there's time, hopefully a few minutes here, tell us briefly about the history of anticoagulation use in pregnancy and postpartum. We know that historically this was one of the major innovations that has helped reduce maternal morbidity and mortality, and we're not debating that. We're just really debating how many women should routinely receive it.
Speaker 3:Right, Okay. Well, heparin was discovered in 1916 by Jay McLean, who was a medical student at Johns Hopkins and working in the laboratory of William Henry Howell. While studying thromboplastins, McLean isolated phosphatide with anticoagulant properties from canine liver tissue, which Howe later refined and named heparin so that's the Greek word hepar means liver. Over the next decade, Howe and his team worked to purify heparin and then better understand its properties, and in 1928, Howe reported that it had an anticoagulant effect. But the early preparations were impure and they caused significant side effects, and so clinical use didn't come until a while later.
Speaker 3:By the 1930s, though, Canadian researchers Charles Best, Arthur Charles and David Scott at the University of Toronto developed a more pure and therefore less toxic form of heparin, and this breakthrough really led to the first human use of heparin in 1935. Breakthrough really led to the first human use of heparin in 1935. And by 1937, it was commercially produced and safely used in patient-centered going surgery. In 1939, the first large-scale clinical trial of heparin was conducted at Toronto General, and again confirming its efficacy and safety as an anticoagulant, and by 1940, heparin had become widely available for medical use, really revolutionizing the treatment and prevention of thrombosis.
Speaker 2:Well, med school used to be really different then. I don't think me or anyone in my class was anywhere close to discovering a new drug in our med school. But you mentioned Charles Best, the Canadian researcher. Was he the one that was also involved in discovering insulin?
Speaker 3:Yeah, I have a good memory and he was a med student when he did that. Yeah, Right. I like insulin.
Speaker 2:Yeah, you do. Well, you might even be addicted to it.
Speaker 3:You use it every day, right? I continuously infuse it in my body.
Speaker 2:Okay, well, coumadin is another blood thinner that is very old as well. It's been around for a while and we don't use it in pregnancy, but it has been used in postpartum patients and has had a generally positive impact against maternal mortality as well. Do you have two minutes to talk about that?
Speaker 3:Two minutes. Here we go, all right. Warfarin was discovered in the 1930s after cattle in North America began mysteriously bleeding to death after consuming moldy sweet clover hay, and they called this, of course, sweet clover disease. In 1933, canadian veterinary pathologist Dr Frank Schofield, suspected that spoiled sweet clover contained a substance that interfered with blood clotting, and this led to further research by Dr Carl Paul Link and his team at the University of Wisconsin-Madison, who successfully isolated the anticoagulant compound dicumarol in 1939. It was first used as a human anticoagulant in 1941, but it wasn't great.
Speaker 3:So there was a desire to develop basically a more potent derivative and in 1945, and this is important with funding from the Wisconsin Alumni Research Foundation, or WARF as it was called, scientists synthesized warfarin. So obviously warfarin is a combination of WARF plus coumarin. It was first introduced in 1948 as a rodenticide, famous rat poison. In 1951, a US Navy officer survived a warfarin overdose after being treated with vitamin K and then that proved its reversibility and somehow, because he survived, its safety in humans, and this led to warfarin's approval for medical use in 1954. They wanted a reversing agent and its adoption then as an anticoagulant gained further attention because in 1955, it was prescribed to President Dwight Eisenhower after he had a heart attack.
Speaker 2:So many questions about this naval officer. Yeah, I don't know what was going on there, but yeah Well, so heparin does not cross the placenta but Coumadin does, and this was known long ago that it could cause birth defects, but it was definitely. It's been used in pregnancy before.
Speaker 3:Yeah, definitely, and I'll put a link to an interesting review article from 1972. If anyone's interested in learning more, it has some of the history of the safety studies and the areas of uncertainty and I'll just read one line from it. Treatment with anticoagulant drugs is probably indicated for the duration of pregnancy in patients with iliofemoral venous thrombosis, recurrent venous thrombosis, pulmonary embolism and prosthetic heart valves.
Speaker 2:Okay, so really not much has changed there.
Speaker 3:Not much has changed, and we still do use porphyrin for mechanical heart valves in pregnant women because the other heparin-based anticoagulants aren't as effective, so even with its risks to the pregnancy.
Speaker 2:So All right. Well, why don't you wrap it up?
Speaker 3:I don't know if that was two minutes or not, but there we go. We'll be back in two weeks with something about pediatric and adolescent gynecology as a teaser. Oh, exciting All righty, we'll see you then, all right. Thanks for listening, all right.