Episode 6.7 Early GDM screening, repeat antibody testing, mayo and more
00:00:02 Repeating Type and Screen for RH-Negative Pregnant Women
00:13:54 Evaluating Early Screening for Gestational Diabetes
00:19:24 Discussing Outcomes of Gestational Diabetes Study
00:27:17 Pelvic Therapy and Vaginal Cleansing
00:37:30 The Controversy Surrounding Preterm Birth Interventions
00:50:58 UK and US Egg Safety Standards
What are we thinking about on today’s episode?
Well, there’s a few new studies to talk about, and one of them is a follow up on early diabetes screening that we had hinted at before, but we’re going to talk about it now. And then there’s also a new study that gives us some information about a predominant theory in pelvic floor physical therapy. Plus, we’ll touch on the use of pessary for preventing preterm labor, and, if we have time, maybe we’ll talk about some other stuff too. We’ll see, but first what’s the thing we do for no reason?
Well, how about doing a routine repeat type and screen at 28 weeks’ gestation before we administer Rhogam or Rhophylac or whatever product you have for anti-D, antibody to mothers?
Okay, well, I have abided by this, I think about 100% in my practice so far. So just as a quick refresher, we do a blood type and antibody screen at the very first prenatal visit to determine mother’s blood type and RH status and whether she has any blood antibodies. And if we find that she’s RH negative and not sensitized, then we can prevent Rh aloimmunization by giving her Rhogam at 28 weeks’ gestation, plus any other time that there’s some kind of event like bleeding or uterine trauma. And then we give it again after delivery if the newborn turns out to be RH positive. And we’ve talked before about how it may not be necessary in the very early first trimester to give Rhogam if there’s bleeding in Rh-negative women, according to at least some society guidelines.
But theoretically we know that sensitization can happen as early as seven to eight weeks, depending on the degree of the hemorrhage. But if the newborn is instead found to be Rh-negative, then there’s no further concern that any amount of blood mixture would not possibly result in Rh-allow immunization. So then we’re done there. But because we don’t have a standard, widespread way to determine the baby’s blood type before birth, then we don’t know that, and so we give at least the one dose prophylactically during pregnancy just in case there ends up being some kind of mixture of blood before delivery. And every time we give a dose it’s thought to be effective for about 12 or 13 weeks. So in a lot of clinics we will repeat that blood type and screen, just like we did at the initial visit, again at 28 weeks, before we give them that dose.
Well, you sound very knowledgeable about this, so you might as well go on and tell us why I think it’s unnecessary, even though you’ve been doing it.
I’ve done many deep dives into this, I believe me, and I’ve thought about it a lot, and I think the argument for doing this type and screen again at 28 weeks is to see if, sometime between her new OB visit and that visit, the mom has developed an antibody during her pregnancy. And that’s also what the ACOG Practice Bulletin cites as well for their rationale for recommending it. Because we know that giving Rhogam to women who are already sensitized no longer has any effect. It’s just completely pointless. And it is possible for that kind of bleed and sensitization to happen without the mother noticing any bleeding or being aware of any trauma. So it’s not necessarily enough just to ask, like you know, have you had any bleeding or did you fall or have a car accident or anything? It can happen even without those events.
Yeah, and then there would be no point in giving them to it if they’re already sensitized. But I think that’s right. But also, though, would it cause harm if you gave them the dose and you didn’t know that they had been sensitized and, more importantly, if you knew that she had a negative antibody screen at the beginning of the pregnancy? What’s the absolute chance that a patient is going to develop an antibody by 28 weeks? In one case series over 1000 Rh-negative pregnant women where they studied that they found that the rate of that was about 0.2%. In other words, two women out of the thousand became sensitized over that time period, and that’s honestly, less than the rate of lab error in a lot of facilities, which ranges from 0.1 to 3%. So I don’t even think that the reason that you stayed in that ACOG States is actually the real reason why a lot of people do this. I think it has more to do with traditional blood bank protocols of requiring some documentation of the blood type and the confirmation of the blood type and need for the medicine before releasing it and administering it, because let’s remember that Rhogam is a blood product, so all of the protocols around administering it released by blood banks, and things like that in the studies and ethical approvals for the trials and things like that would have all of treated this as a blood product.
But, as you said, it is recommended by the US Preventive Task Force Service that you repeat this type and screen at 28 weeks and again, I think that is a legacy of a time when RH disease was much more common than it is today.
The ACOG Practice Bulletin from 2017 does loosely go along with this recommendation, but does say that the cost effectiveness of repeating the test at 28 weeks has been called into question, and they signed a study published in the Green Journal in May of 2014. That was indeed a cost analysis based on a chart review over a 10-year time period that included over 2,000 women, where they found that two women out of 2,029 had serial converted between their negative antibody screen at the new OB visit and by the time they had this done at 28 weeks. Now remember that could have been lab errors at the beginning or at the end, so this is within the margin of error of the lab error. That’s only 0.1% and, based on their model that they built around that data in that 2014 study, in 2014 dollars, they estimated that we could save about $35 million a year in the US by not repeating the type and screen at 28 weeks.
All right, but what about the people that actually did happen in? We assume that they weren’t all lab errors, whether it was 0.1% or 0.2% or some other amount.
Yeah, no, I know what you’re thinking. Well, if you don’t repeat the type and screen at 28 weeks, then you wouldn’t catch that particular patient who has become sensitized during the roughly 16 weeks since her initial OB labs were done and were negative at that time at least. So those are the patients who then might still be at risk of developing hemolytic disease of the fetus and newborn, even though you think you’ve covered them with Rhogam.
Yeah, so by re-screening we can save let’s call it 0.1% of women that serial converted. We can save them from an unnecessary shot, but more importantly, we can identify if their baby might be developing hemolytic disease and then start the management, for that could potentially save them from a really bad outcome.
Right. Well, if it was just about saving 0.1% of RH negative women in previously unsensitized patients from getting an unnecessary Rhogam shot, then I think nobody would be doing this. I mean, I think we can agree on that. It’s literally a harmless shot. The economic savings from not giving those shots is completely eclipsed by the cost of those universal repeat type and screen labs and things like that.
But there’s also no evidence, to get to your point, that we’re saving any babies with this repeat screen, because even for that 0.1% or so of patients who did go from negative to positive and it’s a true conversion something happened during the first or second trimester that caused that. It’s very doubtful that any severe hemolytic disease due to RH antibodies would develop from scratch in such a short time period. You need to have a critical amount of antibodies present for some severe disease to occur and there’s still a lot of variables we don’t fully understand that affect how quickly or severely someone develops an autoimmune response. Historically, before Rhogam, severe hemolytic disease occurred in about 1% of all pregnancies, despite there being much more than a 1% chance of RH negative mothers carrying RH positive babies, and almost never did it occur in the initial index pregnancy, the first pregnancy.
Yeah, because we know that IgM, which is the first antibody that’s formed with an exposure, it cannot cross the placenta. So she would need repeated exposures of the same thing to develop the IgG antibodies which do cross the placenta and are what causes the hemolytic disease in the baby. And yeah, you’re right, we don’t know exactly what is the possible range of timelines, for how long it takes to go from IgM antibodies against the D antigen to IgG. But generally someone exposed during one pregnancy doesn’t end up making any IgG, or at least nowhere near enough to cause harm, until they’re re-exposed in their next pregnancy. But in that case then you should detect those antibodies right away in their first initial labs of that next pregnancy and you would know early on and follow the titers. We wouldn’t even be talk, we wouldn’t even be re screening them at twenty eight weeks.
Yeah, that case and I think we can sit here for a whole season of podcast and come up with incredibly rare scenarios and diseases that that we wouldn’t argue, that we should screen for, even though they can be bad. Yeah and so we’re creating something that’s incredibly unlikely. And then is the question is that we’re screening thousands, to hundreds of thousands of women to find one, or millions perhaps, to find one case.
Now there was a case report, of course of an adult rh hemolytic disease that occurred in a patient in Malaysia in twenty nineteen. This is a primer gravity patient who had no known sensitizing events prior to delivery. Now, of course, that being said, her first test might have been an error. We don’t as a problem stuff like this, we don’t know that. But that case has other holes in it. So they the lab had misidentified her as being rh positive at her new will be labs, they know that. So her care started off with a lab error.
Secondly, it doesn’t look like she ever had an anatomy ultrasound. Her second time she got a blood draw was at the time of delivery, when they finally just identified her as being rh negative and also noted a significant high anti-de-titer, much higher than you would see after Rogan, although there aren’t strict cutoffs for this. So even in this case, we can’t prove that she was actually unsensitized at the beginning of a pregnancy and it’s probably likely that she was. So, yeah, there might be some theoretic possibilities, but we shouldn’t call that evidence. And even if you accept this case, it’s probably spurious. We’re still talking about one out of many. What? Tens of millions, hundreds of millions.
I mean, it’s just rare, yeah. So basically what you’re saying is doing a routine type in screen at twenty eight weeks of at least of all rh negative women is only for the theoretical benefit of some fraction, tiny fraction of point one percent of rh negative patients.
Yeah, I think it would be reasonable, of course, to always do something on a case by case basis. Use your clinical judgment we were talking about this before we started recording about hypertension, where the guideline doesn’t fit every situation. Use your common sense, be a doctor, use your clinical judgment. So if you had a patient that had some event that could have caused a large fetomaternal hemorrhage early in the pregnancy and they hadn’t already been given Rogan for it or something at the time that it occurred, okay, well, sure, recheck it. That perfect, that’s fine. That would be a tiny minority of patients.
I’ll say that the US British Task Force guideline, which ACOG kind of relies on, was written in 2004. And so I think it is another example of a guideline being out of date. It’s almost 20 years old. Acog waffles on this. They put their wording in there. After that article we read that we talked about in the cost analysis, but the evidence they cite in the bulletin says the practice is not financially valuable. So Backburner guideline that hasn’t been updated in 20 years, and we have a few more of those to talk about in a few more episodes coming up of these older guidelines that there’s plenty of new evidence and they need to be changed.
Yeah, and that’ll probably come up again in this episode, where there’s a. Yeah, guideline based on what seems like common sense, but then has failed scientific scrutiny, but still remains the guideline nonetheless.
Well, that’s the most immediate foreshadow. That’s not a foreshadow, that’s a segue. Okay, so let’s just get right into what we’re talking about. Is this idea about early screening for gestational diabetes in obese women?
All right, yeah, let’s do it. We’ve previously talked about this. Since 2013, ACOG has recommended early screening for gestational diabetes you could call it early gestational or you could call it pre gestational diabetes among women with certain diabetes risk factors. It includes a specific list, for ACOG at least, and it’s specific but also pretty broad. So, for example, anyone with a BMI of 25 or higher who is sedentary.
So not the athlete, the crossfitter with a BMI of 28, because she’s fit.
Right, or if they’re of Asian descent and their BMI is 23 or higher and they’re sedentary. And then also anyone with morbid obesity, regardless of how active they are or any other factors that are either favorable or not favorable. If they’re morbidly obese, then they also would fit that. And up until and there’s a bunch of other, I won’t list them all that it’s in the ACOG practice bulletin, but up until 2020 there had been no studies that evaluated whether or not this was beneficial to use this list and screen these specific women early in their pregnancies. But, as we previously mentioned, there’s a trial published in the great journal in May of 2020 called the ego trial. That that does answer this a little bit, yeah.
I think we had to be careful with these sort of recommendations based on theory or expert opinion or common sense, because, wow, you could screen all kinds of people there and well, what’s the harm in screening?
I can hear the arguments, but it’s not scientific unless you have scientific data that supports it. So the ego trial they took women with BMI is greater than 30 and randomized them to either early screening between 14 and 20 weeks or just routine screening, as we would normally do, between 24 and 28 weeks. Now they randomized a total of 962 women who had similar baseline characteristics and they found that early screening did not reduce the incidence of the primary outcome, which was actually trending towards being more common in the early screen group than the routine group. The primary outcome was a composite of adverse perinatal outcomes, including any one of the following macrosomia, primary cesarean delivery, hypertensive disorder, shoulder dystocia and neonatal hypoglycemia or neonatal hyperbilirubinemia. The only thing that was different between the groups was that more women in the early screen group were put on insulin, but the management didn’t seem to make a difference in any of those important outcomes. In fact, again, the trend was towards more adverse outcomes in the early screen group.
Well, that is interesting and, as I just listed, technically the BMI of 30 alone doesn’t meet ACOG’s recommended criteria to do the early screening For them. It’s BMI 35 alone or higher, and that’s probably splitting hairs a little bit.
Right, so you would be focusing on the sicker patients or the more at-risk ones, so you wouldn’t be, concluding, the less sick, less at-risk people would make a difference.
Yeah, yeah, and I’d be interested to know because I haven’t looked this closely at it if they included any kind of breakdown of patients having additional risk factors, so whether they also were physically inactive or family history or PCOS or something like that.
Now, actually, there’s another new child that does pull some of that in, because in the New England Journal of Medicine on June 8th of 2023, Simmons and colleagues also published a study. It was done a little bit differently than the EGO child. They recruited women with at least one risk factor for gestational diabetes, so not just BMI. They used their own list that somewhat overlapped with the ACOG list. They had all of these women do an early two-hour glucose tolerance test before 20 weeks of pregnancy and then, of those women who failed it early on, those women were randomized either to receive immediate treatment for diabetes and they were treated as gestational diabetics, or the other group only got treatment later on if they then also did the routine 28-week glucose tolerance test and failed that one as well. And of course, that also was a two-hour instead of a one-hour.
Right. So right away, though you can see, this was also very broad and probably included a lot of false positive diagnoses. One of the risk factors they included was simply non-European ancestry, for example, and that gets you to the Asian example too. Perhaps the others were prior gestational diabetes or macrosomia, pcos, a BMI over 30 or age over 40, or even just a first degree relative with diabetes. If you think about it, that encompasses the majority of patients in the United States. I would think it’s almost not much different than universal screening when you include all of those risk factors, and we also know that the two-hour GTT tends to overdiagnose gestational diabetes as well, compared to the one-hour GTT followed by a three-hour that we use more commonly in the United States.
Yeah, so this more recent study took a pretty aggressive stance on screening. Their treatment, though, was pretty conventional. They described an education program with dietary advice, home glucose monitoring and then medical therapy if blood sugars were out of range. And of course, it also included more intense monitoring of their newborns blood sugars if the mothers ended up being in either of the treatment groups.
Yeah, at some point you have to ask, I think, the question of what amount of hyperglycemia in pregnancy is normal. Pregnancy does make mothers more insulin resistant and that’s necessary physiologically to help support fetal growth. So we have to be careful when we pathologize it and make sure that we’re not overdiagnosing glucose intolerance. One of the hardest things we do in medicine I tell my medical students is determining between variation and deviation, and this is a great example of that. When is this abnormal? When is it pathologic? Now, I know it probably doesn’t sound too harmful, but how would you like to be checking and logging your blood sugars four times a day and restricting what you eat when you didn’t have to, let alone potentially starting medicine, insulin shots that you didn’t need to start, and then having your newborns baby sugars checked more often than they needed to be because of over testing?
essentially, yeah, I mean that would suck. I wouldn’t want that. I wouldn’t want that for my patients either, but I guess it would be worth it if all of that actually helped. So now we should discuss the outcomes of this study by Simmons. Like the EGO trial, they also looked at an aggregate of neonatal complications as their primary outcome, and that included preterm birth weight greater than 4,500 grams, birth trauma, neonatal respiratory distress, need for phototherapy and either stillbirth or neonatal death and shoulder dystocia. And then they also had some secondary outcomes they looked at. That included maternal hypertensive disorders or need medical need for labor induction or cesarean and perineal trauma, and then also some neonatal body fat mass and blood sugar parameters.
All right, and what did they conclude?
Well, in their conclusion, if you look at the very, at the abstract, they concluded that there was modest benefit, in their primary outcome at least, and that was based on a fairly statistically significant difference only in that aggregated primary outcome. But read on later in the paper they did point out that there were no differences in what they called material outcomes and they seem to actually try to emphasize that they didn’t find any meaningful differences in clinical outcomes.
Yeah, I had a lot of respect actually for the way they did that. If you look at the breakdown of those outcomes, there were no differences in things that probably matter the most, like preterm birth, hypertension, birth trauma, need for phototherapy, rate of still birth or neonatal death, risk of shoulder dystocia, need for a cesarean delivery or any outcome that we would typically think of when we’re trying to treat gestational diabetes and make a difference in outcomes. So the difference in the two groups came only from a difference in neonatal respiratory distress.
Yeah, that and that was part of the aggregate, so then that essentially applied to their entire aggregate and they commented that finding was unexpected. Even though they did include it, they noted that other trials have not shown that treatment of gestational diabetes makes a difference in neonatal respiratory distress specifically.
So they acknowledge that this essentially was a negative trial, aside from the fact that this finding of respiratory distress was there and this was a novel finding that hasn’t been replicated, and the risk in looking at so many different outcomes is at least one of those outcomes will be a type one error and in this case I think, as I said, they did a good job of not claiming that they found something important and acknowledging that this might be a type one error and not something that really matters to patients. There’s also, by the way, in accompanying editorial in the same edition of the new England Journal of Medicine that reviews a study and puts into context both of these studies we’ve been talking about and says that this new paper should call into question the current recommendation for early screening.
Yeah, so I think it’s fair to say that early screening, at least after reading this paper, early screening based on these, this wide categorization of minor risk factors does not prevent Large for gestational age babies or birth trauma or any of those other things that we typically worry about with gestational diabetes. And really these two studies combine don’t seem to support early screening for most women at least.
Right and, importantly, it’s not like there are other studies that do so. That that’s the important thing. So I think this is another area where the recommendation is out of date and is mainly based on what was felt to be common sense rather than hard data, and we’ve seen how often these kinds of recommendations last way beyond the time the data comes along to repudiate them. So we’ll just have to see how long it takes for this non evidence based practice to stop as well.
I guess we’ll have to decide, either as individual doctors or even within our local groups, whether we follow the guideline to a T because it’s a cogs guideline, or do we shift towards Early screening of just a more carefully selected, higher risk group of patients, like maybe those with BMI is over 40 or 45, or with sure yeah with multiple risk factors people really think have pre existing diabetes.
Yeah, yeah, or just don’t screen anybody. Some people may also take away from this child that rigorous early glucose screening of a lot of people will at least help decrease the rate of neonatal respiratory distress. But that wasn’t the reason why the recommendation was made and again, that finding hasn’t been replicated. So I think that would that argument would be more just grasping at straws.
Yeah, moving the goalpost a little bit yeah and if people listen to this podcast regularly.
If anything should have learned by now, don’t change your practice based upon one study or one finding in one study, because they almost never Pass replication. There are exceptions to that, but this isn’t one of them. So, and more importantly, respiratory distress that thing probably isn’t even true, since, again, it hasn’t been found in other studies that have looked at it. It’s not like it’s the first time it’s been looked at. But even if it were true, this was represented a very minor and transient diagnosis for these newborns and almost all cases, and wouldn’t justify the enormous cost associated with the intervention.
Okay, well, I hope this spurs new reviews of the guideline or maybe new studies or something.
So we’ll have to see how that unfolds yeah, well, people are still waiting on the cage match between you and me about public for physical therapy. And we don’t have time for that today, but there is. There is some stuff to talk about before we get into the real shouting match.
I don’t know if I don’t think the audience likes us to fight the ratings or though, so I don’t know, maybe they do okay we could pull in new like the worldwide wrestling people okay do you want to?
give to go.
Well, that it’s up to you.
Well, I’m afraid of you, so okay.
But I will say that there has been a lot of. There’s a lot of literature coming out. You and I both have been deep in this literature preparing for the octagon and a lot of stuff out there, and I’ve seen some things coming out of the public for physical therapy world at least where I practice that Are claims that are just far less than scrupulous, and I think that’s part of the issue is that you see it abused in people making nonscientific claims about public for physical therapy and then sometimes that overshadows the real benefits and that’s where we have to get into the weeds. But it seems like an increasingly elaborate theory is catching on that public for muscle disorders are related to all sorts of different medical problems and health conditions. So it’s turning into this expansive sort of therapy creep or indication drift, if you will, for what public for physical therapy is good for, and patients are being encouraged to do public for physical therapy for all sorts of reasons that we never even heard of five years ago.
One hard part about this whole discussion is that the evidence is difficult to interpret to begin with, because some of the outcomes, at least, are necessarily subjective and patient reported, so they have to be very carefully validated. But I think I also have seen claims being made, at least recently, about benefits that have not even been studied at all, and I’d love for some of those things to be true and just be able to say oh, actually, pelvic floor therapy can help you, let me just send you on over there and it’ll get all better, and I’m sure my patients would love for that to be true as well. But For some of those claims that really would just be dishonest. So I’m curious what sort of things have you heard or seen?
Yeah, I have screen caps of these things, but I think in some cases in a lot of cases are just taking credit for what happens naturally in the postpartum period. So, for example, preventing tears and subsequent births. Most women don’t tear in subsequent births anyway, or at least not as extensively as they did in the first one, and the idea of stretching the vagina or vulva to prevent tears just likely leads to long term pelvic floor dysfunction. At some point we need to do a deeper dive into whether there is a preventative role in pelvic floor physical therapy against future pelvic floor dysfunction or how helpful it is for structural issues like stressing continents or prolapse. Plus, what’s the appropriate role of physical therapy in the treatment of pain with sex or dyspareunia and things like that?
Those are specific examples where the effects of physical therapy have been studied and we can discuss the strengths and weaknesses of that evidence and how good it is or isn’t. But I want to call out things like prescribing pelvic floor physical therapy for children who have constipation. I see that it reminds me of chiropractic manipulation of newborns. The pelvic floor has just become the source of all issues, including issues not even in your pelvis, and it’s in. People talk about it being related to the concept of increased tone of the pelvic floor muscles or overactivity of the pelvic floor muscles, and then that’s argued again to be related to all sorts of conditions in people of all ages.
Yeah, I guess it’s that idea that if you have a hammer, then everything looks like a nail. So, like for the chiropractor, they think any disease has some contribution from a subluxation that they can fix. And then now here, for at least some of those more social media active physical therapist than their nail, is pelvic type, pelvic floor, muscle tone Right.
I see some fundamentally incorrect things about this on social media, especially, as you said, from some of the influencers, like the idea that a strong pelvic floor muscle assist in childbirth, as if those muscles somehow are the ones that push the child out. They want to exercise to help you push the baby up, when in fact they should be relaxed. Or that back pain and other upper body problems are supposedly caused by tension in the pelvic floor. That were tensions there. A lot Hemorrhoids are claimed to be related to tension in the pelvic floor muscles. Infertility is related to tension in the pelvic floor. Urinary frequency and overactive bladder, or even bedtime wedding at night when children are all supposedly related to tension in the pelvic floor.
Yeah, it sounds like a solution that’s in search of a problem like those as seen on TV products, and a lot of those sort of claims are way beyond anything supported by literature, and I think it’s unfortunate to see yet another discipline that does really good things and in some cases, is vital for that to be invaded by all these nonscientific ideas.
Well, unfortunately, that’s the natural order of things. It’s no different for OBGYN or cardiology or anything else. But the reason we bring this up is there’s a new systematic review in the June 2023 Gray Journal that looks at evidence about the concept of increased tone or overactivity of the pelvic floor muscles in various pelvic health conditions, and this was written by pelvic floor physical therapists and they really just examine the idea of whether overactive or hyper tonic pelvic floor muscles are even related to genuine pelvic floor conditions such as pain or incontinence or things like that.
Ok, so what did they find?
Well, essentially, they found that no connection established in the scientific literature. There’s not a distinct difference in the tone or activity of pelvic floor muscles in patients with or without many of the conditions that pelvic floor physical therapists treat, and so therefore, the paradigm or the model, the framework of muscle tone or muscle hyperactivity isn’t scientific.
I think it’s nice that they’ve focused in and clarified this point, because I think the theory of just globally high muscle tone in the pelvis that just needs to be relaxed somehow is really a gross oversimplification of what’s happening in most cases, especially pelvic pain, but really a lot of other conditions too. So did they conclude that there’s no connection because there’s a lack of appropriate studies?
No, they commented on just how much data there is. They looked at 151 studies using eight different types of tools that were meant to measure tone or hyperactivity, and they just couldn’t find evidence that this pathophysiologic mechanism or understanding is valid.
I see how it’s tempting to blame a lot of really these are really challenging conditions on just one easily measurable physiologic parameter. So, yeah, there’s all these tools to measure tone in the muscle. It’s easily measurable and it would be nice if it was true. But we know already that pelvic pain, for example, is multifactorial and often takes several different approaches working together to properly manage it, and some okay. Someday in the future we can get into a cage match, I guess, about what physical therapy is good for and not good for. But this review is more of a commentary on the mechanism of disease and understanding how it might work.
Right, it wasn’t a commentary on whether or not the physical therapy itself, whatever it’s doing, is useful for it, but things that address this paradigm of tone or tonicity or something may be the problem. So, like the subluxation in chiropractic care becomes, as you said, the nail for their hammer. But that subluxation, by the way, doesn’t exist.
It’s something that has been studied ad nauseum. It’s not an identifiable on imaging or there’s no tool that exists that can identify it. So it’s important to understand that purported mechanisms affecting various health conditions related to tone are likely to be false. Another example is blaming a bunch of different elements on TMJ, which then is just elevated tone in the jaw, and it’s not that TMJ isn’t a real thing, but it’s not the cause of systemic illness in your body.
Well, in that same edition of the Grey Journal there was a different study. There was a randomized clinical trial looking at vaginal cleansing before unscheduled caesareans to reduce infection, and this is something we’ve also talked about a little bit, at least on the podcast. I’ve talked about it a lot in my own practice. I’ve gone to journal clubs on this and I’ve actually heavily advocated for it in my own departments, just based on studies in the past. But in this particular trial they randomized 608 women who had non-elective or unscheduled caesarean deliveries. So basically, caesareans after labor had started to either getting the vaginal cleansing or not and they found no improvement in surgical site infections and in their conclusion they recommended against vaginal cleansing in this setting.
Yeah, I think this was maybe one of the more important articles in that edition. This is something that’s been looked at scheduled caesarean deliveries when you have intact membranes in non-laboring women and some data has indicated that it was effective. So it seems like it would be a no-brainer to extrapolate that to women in labor or women who’ve had their water broken, who likely have a much higher amount of vaginal bacterial exposure into their abdominal cavity and abdominal wall, particularly if their water’s broken. But it’s the clinical evidence that matters, not common sense, and this is an excellent study that clearly showed no benefit of prepping the vagina before caesareans for women in labor.
Yeah, I’ve been trying to wrap my mind around that. I guess in a way it can make sense, because once they’re in labor with ruptured membranes, maybe by then it’s too late, like the bacteria’s already gone up and if you just cleanse the vagina then you’re not gonna get to where it actually is. And that’s why we already know to give a systemic dose of azithromycin, usually in those settings, and that actually does help and I suppose in a way this is good news, because it’s also not very convenient to have to do that vaginal prep in the setting of sometimes a very emergent delivery like hey, hold on one sec while I put this sponge in here. But I’m still wondering whether it can help in the setting of chorioamnionitis, for example.
But I’m guessing by then it probably is too late for just that localized cleansing to help and that patient’s going to be on other antibiotics right or chorio, that may overpower.
I mean clinda or something else. It has the same effect so yeah okay.
well, there’s a very important article in the July 25th edition of JAMA.
This is a result of the TOPS randomized controlled trial TOPS by Hoffman and colleagues. That was designed to see if a cervical pessary was effective in preventing preterm birth in patients who had a shortened cervix. There’s also an accompanying editorial called the vexing problem of preterm birth prevention, which I think does a good job of studying the three seconds. There’s also an accompanying editorial called the vexing problem of preterm birth prevention, which I think does a good job of outlining the frustrations with various remedies over the years that focused on treating and preventing preterm birth that haven’t worked out. So it discusses things like 17-hydroxyprogesterone caproate, tocolytic drugs and other interventions like vaginal progesterone, for example. Everyone wants something to work here and as we identify risk factors for preterm birth, like a history of prior preterm birth or a cervix less than 25 millimeters or maybe 20 millimeters or some number in the current pregnancy, then we just keep throwing everything in the kitchen sink at these patients to see if we can do something, and all these things just keep ending in failure.
essentially, yeah, that editorial talks about how, despite lots of efforts with patients with shortened cervix like vaginal progesterone or cerclage or cervical pessary we haven’t really seen any difference in the rate of preterm birth or obstetric outcomes or neonatal outcomes. And any improvements that we have seen related to preterm birth, at least in the US, really belong to the field of neonatology and we’ve talked about a lot of these things on the podcast before. And initial data usually from smaller, poorly designed or underpowered studies will show some benefit from some intervention and then they become quickly established into our routine and into the armamentarium of high-risk doctors until later on larger, better studies show that they actually didn’t work. But by then people are already using those interventions and they don’t stop using them and we talk about that whole phenomenon a whole lot on here.
The perspective of the editorial is very blunt in that overall, none of these interventions that have been studied have affected the rates of preterm birth in the US and if any of them actually were able to reduce the rates of preterm birth, we would have seen a difference by now. We would know it for sure. There wouldn’t be mixed data or controversy on it, but for the ultrasound discovered short cervix pessaries have been used and again based on weak initial evidence. Now we have the Tops trial to put the stop to this once again more definitively.
You’re giving away the results already. Maybe it worked.
Maybe it worked Okay.
Well, I will say, though, that editorial does give a good perspective. So just think about 7-Hentroxyprogester-Encap rate, just for a second. We spent 15 years nearly in the United States throwing 7-Hentroxyprogester-Encap rate at every woman we could identify, and you can say what you want to about individual studies or this trial or that one, the birth rate didn’t decline, the preterm birth rate didn’t decline. So ultimately we did make a difference, and I would argue, of course, that the individual studies agree with that, but some would disagree, and that’s another perspective that this editorial offers. So, yeah, pessaries, though for preterm birth prevention is nothing new.
In the 1970s there was a pessary called the Arabin pessary. That was specifically designed to treat preterm birth or prevent preterm birth, and it’s been used by a lot of doctors as an alternative to cervical cerclage. So in many cases there’ll be a small case series and other small reports that show that it was equivalent to cervical cerclage. But unfortunately, that might be like saying that magnesium sulfate was equivalent to IV alcohol for prevention or treatment of preterm birth. We need a placebo trial, not a comparative trial. So we’re starting with an assumption, then, that cervical cerclage in those patients was effective, and cervical cerclages are not nearly as effective for patients, as we once thought they were, and the indications for cerclage were much broader in the 1970s than they are now.
The McDonald’s original cerclage was in women in active preterm labor, not women with a history of loss. They thought it would help, but over time we’ve progressively narrowed those indications. Now there was a small trial published in the Lancet in 2012 that showed that for women with a short cervix, the Arabin pessary was associated with a reduced rate of preterm birth, but then a study published the next year in the American Journal of Perinatology showed that it wasn’t. And this is a story of a lot of these interventions where studies disagree with each other. For a few years, small studies and the effects appear minor, and the truth is the studies are just not well designed or, again, insufficiently powered to answer the question.
Right. So the top study. The intention was to, I guess, break the tie and again answer this question more definitively. They randomized 544 women to either a pessary between 16 to 23 weeks or to usual care, and almost all of the patients were receiving vaginal progesterone as well, which was the treatment that was originally found to be effective for shortened cervix and is mainly the reason why we even started routinely measuring cervical lengths in the mid trimester. To begin with, everyone in the study had a cervical length of less than 25 millimeters during their anatomy scan, and this means that they should be patients who are at a significantly higher risk of preterm birth.
Right and they found that the patients who were randomized to a pessary had a 45.5 percent risk of a combined outcome of preterm birth or fetal death before 37 weeks, and that this was no different than the patients who had usual care, and the number was 45.6 percent. So, however, they did find that fetal or neonatal or infant death occurred more frequently in those receiving a pessary, at a rate of 13.3 percent, compared to those randomized to usual care, where it was only 6.8 percent risk of death, so more than double the risk of death in the pessary group.
That was a new finding that had not been seen in those smaller previous studies, and they do note that most of those deaths occurred prior to a viable gestational age. But regardless, the institutional review board ended the study early because there was both no improvement in outcomes and then there was also this disturbing trend towards increased risk of perinatal death.
And, just like the decreased respiratory distress rates in the gestational diabetes early screening group, that’s probably not a real finding. People need to not get caught up in novel findings of subgroups. Nevertheless, it wasn’t benefiting them, so why take the risk? So they ended it. But I’ll say that for me, this should be the end of the use of pessaries for prevention of preterm birth or treatment of threatened preterm labor. Of course it won’t be, and many of the doctors who’ve been using them for years will continue to do so despite this new evidence. Just like with so many other interventions that we’ve talked about, I think one of the rules of thumb that people should take away from medical literature is that when there are mixed studies meaning some studies show no benefit, some studies show a marginal benefit then usually the truth is there’s no benefit. It’s very easy to show some degree of marginal benefit from data, particularly if it’s diced and sliced and dissected in the right way, and researchers are tempted to do this. Remember that the false discovery rate in most clinical trials is as high as 80%, and a lot of that is due to poor statistical methodologies or poor study designs, or p-hacking for that matter. But that’s why we need replication. In this case, we now have two good studies that say that this doesn’t work and any small contradictory studies before that. They don’t add up to some evidence that can trump these two or even just this one good, high quality study.
The finding of an increased risk of death is interesting and maybe it’s false. It might be explainable, though, by an introduction of a foreign body in the vagina and for some patients maybe that led to an increased rate of infection. This is an issue that you might expect. This is one of the problems with cerclages. I don’t think we can draw those conclusions from this and I don’t think we should, but we do know that’s true of cerclages.
We know that when there is a stitch in the cervix that the risk of preterm rupture of membranes is nearly quadrupled due to quarry, to sigil, inflammation related to the foreign body and infection risk and things like that. So cerclages probably cause some preterm burst due to that inflammation, but they also might prevent others. But on the whole, on the balance, the risk and benefit it weighs out and for most indications they don’t seem to make a difference. That might also be the case with the pessary, but we have to look at outcomes that matter and the outcome that matters is whether or not you have a living child at the end of your pregnancy, whether that’s 37 weeks or some better preterm gestational age, and the answer is that the pessary doesn’t make a difference, so we should stop using them.
Well, it’s good news to me because I’ve never used them and I think the only time I’ve even anecdotally heard of one of my colleagues a high-risk colleague using it didn’t work and really the idea of slipping this round hoop object around the outside of the cervix like a little belt and just hoping it stays in place really seems iffy to me because I can just picture the cervix just retracting back out of it.
But anyway, the appendix of this study does list each of the individual deaths that occurred in both groups. So there were 18 fetal deaths or stillbirths and 19 neonatal or infant deaths after birth in the pessary group, and this was compared to nine fetal deaths or stillbirths and nine neonatal deaths in the usual care group. So most of the early infant deaths in that pessary group occurred because the baby was born prior to viability, usually with hour-glassing membranes and chorioamnionitis and active labor. And that was also true in the usual care group. But in that group there was only one case of chorioamnionitis compared to three cases in the pessary group and, more importantly, twice as many patients presented with labor or hour-glassing membranes in that pessary group. So I think that that could maybe support the theory that pessary increases the rate of inflammation and infection. It is a very small number to compare, so it’s hard to definitively conclude that.
Yeah, the infant deaths were basically the same story. In the usual care group, of those nine neonatal or infant deaths, all of them were before 24 completely weeks and they reported one case of chorio. And in the pessary group, of the 19 infant neonatal deaths, all but one were before 25 completed weeks. The outlier was a 27-week three-day newborn but there were six cases of chorio in the pessary group and obviously more than double the total number of losses. So it may be a similar underlying process going on. It may be something that fails replication and, importantly, I’m open to the idea that that’s not true. I believe in replication in science.
It’s also a good lesson that sometimes stopping labor that is progressing particularly early in pregnancy even if we actually had the true ability to do that may just lead to higher rates of infection. So you’ve pointed out before that, even if you could stop labor at 23 weeks, that 23-week labor often is due to infection. So all you may be doing is producing an infected uterus and an infected 23-week three-day newborn instead of having a non-infected uterus and a non-infected infant that’s three days younger right at 23 weeks. So arguably, being slightly more mature at birth because you had some effective intervention to delay the preterm birth might not be worth it if it also means that you’ll be born septic.
Yeah, yeah, and that’s the point that people miss. We have to think about total outcomes that matter, and just because you don’t know the mechanism by which some harm may occur from what we do doesn’t mean there isn’t one, so we have to rely on empiric data.
Well, I’ve had a burning question, but I don’t know if we have time to talk about it. Maybe we’ll.
We have a few minutes, I guess, okay.
Well, is this about UTI? As you said, it was a burning question. I don’t know, not quite.
No, it’s actually going back to our prior discussion a long time ago about sushi. So should pregnant women avoid mayonnaise?
mayonnaise. What do you mean?
You haven’t heard that one.
I mean, okay, we were watching that show, Ozark, and I saw a line about mayonnaise and pregnancy that I thought was just poor writing or a gag. The pregnant lady said that whatever doctor she saw said she couldn’t eat mayonnaise while she was pregnant and that this doctor should lose his license for being so offensive because she had a craving for mayonnaise. But that’s my extent of the mayonnaise dilemma.
I mean, sometimes it’s the mayonnaise in a sandwich that just hits right. That’s right, especially for a pregnant woman. So it is definitely a thing out there on the internet. I haven’t seen it on anything that ACOG has put out, of course, but I think the issue really is homemade mayonnaise made with raw eggs rather than the commercial mayonnaise that you would buy in the store.
That’s made from pasteurized raw eggs. Right, that makes more sense. So I know that Julia Child would always make her own mayonnaise, but I don’t hear of a lot of people making their own mayonnaise at often anymore, but I suppose some foodies do.
Well, yeah, I think some foodies may still make their own mayonnaise Maybe it’s more common in rural areas or they might also make other similar creamy sauces that use raw eggs, like hollandaise or tartar sauces, horseradish or bairnay’s, and raw eggs are also in some other really delicious things like mousse and tiramisu.
I don’t know what half the things you just said. Would you consider yourself a foodie?
Well, I eat food, so I guess, if you are what you eat, I suppose that would make me a foodie.
Well, you know what bairnay’s is, so okay. Well, what’s the problem with raw eggs?
Well, it’s salmonella and we talked about that with sushi. So it’s not that the salmonella would cause a birth defect or miscarriage, but it can make you very ill and give you really bad diarrhea and vomiting and stuff when you’re sick. So it’s that same food poisoning debate. Like we want to avoid that, especially in pregnancy, just so she doesn’t get dehydrated and stuff. And in the 1980s, due to some public health scares, people were concerned that a lot of eggs might be infected with salmonella. And then women were taught to avoid anything with raw eggs, but also even just soft-boiled or runny scrambled eggs, due to the concerns about salmonella. And in general people were just told not to eat raw eggs, even though prior to this whole campaign it was considered okay, I think everything I know about food concern television.
I do remember when I was a kid watching Julia Child, but also Rocky, and I remember the original Rocky and he would make a cocktail that included raw eggs to get more protein, I suppose, and other myth, and I even remember I would do that you would mix raw eggs and tang when I was a kid. And then I do recall at some point in my life I was told that I shouldn’t eat raw eggs anymore and frankly, I’ve been mad and just generally unhappy ever since then.
Maybe bring that up with your therapist. Anyway, in 1990, in the UK, the Food Standards Agency declared that British lion eggs were safe to eat, even if they were raw, even by pregnant women and young children, and this was related to increased hygiene and storage and transportation standards associated with that type of egg and also vaccination programs for British hens.
Okay, British hens have different accent than American hens. I don’t know. I’ll look for it. That’s useful to know if I’m ever in the United Kingdom, I suppose, and pregnant at the same time. But what about the United States?
Well, in the US all eggs are actually required to be washed with warm water that’s at least 90 degrees Fahrenheit, and they also have to use a detergent, and then they have to be rinsed with a chemical stainer that removes any bacteria, and then they have to be dried, of course, so bacteria cannot penetrate a thoroughly dried eggshell that’s intact. So the US actually has a higher standard for egg hygiene than the UK did, and the UK created their higher grade eggs basically because of their salmonella problem, where these routine policies were not being carried out. And in fact, eggs in the European Union are not allowed to be washed. They’re also shipped and stored in an unrefrigerated truck and on just the regular shelves in the store, not in the refrigerated shelves. But of course eggs in the US are refrigerated.
The EU law actually forbids refrigeration of eggs and there’s been a debate about this in terms of what the impact is, not just for salmonella but other bacteria as well. But this is what led to widespread vaccination against salmonella in the chickens in the UK in 1990s. They basically have no egg-borne salmonella in the UK anymore, but in the US only about 90% of eggs come from hens that have been vaccinated, because vaccination is voluntary on the part of the manufacturers, so they previously pretty much avoided it due to the cost. But as long as the egg is refrigerated, even if the hen is not vaccinated and there’s a bunch of salmonella in there, the refrigeration would inhibit that salmonella growth and since 2010, the federal rules require at least testing for salmonella among hens. If not, they don’t require vaccination, but at least testing. So that also has been helpful to reduce the incidence.
Okay, so we refrigerate in the United States because we don’t have a 100% chicken vaccination rate, I guess. But I guess we also don’t have any assurance about the supply chain, since this isn’t a universal requirement and we still certainly do have salmonella outbreaks in the US from eggs. This is also why we said in a prior episode about sushi that you’re significantly more likely to get food poisoning from cooked chicken than from raw sushi, and that’s because of the prevalence of salmonella in the absence of universally mandated vaccination. So can’t we just buy eggs from hens that have been vaccinated if we want to eat them raw? Or here’s an idea make the vaccine available to humans?
so we can just eat all the chicken and eggs we want, with immunity.
Well, that’s a clever idea. I don’t know if a human could get their hands on a vaccine, but maybe. But I’ll let’s just.
I don’t think that’s actually a possibility right now I want my tang and chicken, tang and eggs, tang and eggs.
Well, you can check on the individual brands as you see them in your grocery stores and see if you can do some Google search and see if they come from a producer that vaccinate their hands, and usually if you just look at the carton then you can find out a lot of information by doing a little internet search.
Yeah, so really, then, the people at most at risk are those who are either producing their own eggs, and probably in unvaccinated hens, or buying them locally at farmers markets from unvaccinated hens, or perhaps people who are buying eggs specifically from producers who say we don’t vaccinate or do anything. Maybe they don’t vaccinate for salmonella too. Those eggs are might be less likely to have been washed, also the locally produced ones or the ones in your own backyard and the hens also not vaccinated. So the people at most risk are the ones who might think they’re doing something kind of natural, I guess.
Yeah Well, I haven’t gotten out to farmers markets as much as I would like, so I’ve never bought eggs from a farmers market before and I wouldn’t want to discourage someone from supporting local farmers. I suppose you could go to the farmers market and just ask the vendor what do you do with your hens and what do you do with your eggs before you sell them? And I also want to clarify that when you go to certain food stores that have a bunch of free range or certified humane eggs, those are not unwashed. They’re not at any higher risk for salmonella than the mass produced kind you might get at, like Walmart, for example. We like to buy those ones that say happy hen or whatever, and there’s a lot of different brands that do that and they emphasize that the hens can roam around. That has nothing to do with salmonella. But anyway, those egg cartons do say what standards they comply with, and often those include requirements to test and or vaccinate their hens against salmonella.
And earlier we mentioned the pasteurized eggs that are in store bought mayonnaise. So just another tidbit about that. All food products made using eggs in the US, which are usually made with raw eggs, are required to have those raw eggs pasteurized, but that’s not necessarily done with the eggs still in their shells. It is possible to pasteurize eggs in their shells, but it’s a lot more difficult to do that without accidentally cooking them and turning them into hard boiled eggs. So it’s, of course, not a requirement for the just the eggs you buy in a carton that are raw for those to be pasteurized, because, as I said, it’s difficult and you might get the accidental hard boiled eggs in there Sometimes you will see that actually but those ones they’re actually not required to be refrigerated.
If they’re a rare, raw egg that’s been pasteurized, then they don’t have to be refrigerated. I don’t know if I mentioned in the prior sushi episode, but pasteurizing eggs like it uses heat and so it can be done on an industrial scale, on a large scale. They use like a really specific method. But if you try to pasteurize eggs at home you’re just going to end up cooking them, so you might as well just cook them instead. Anyway, hopefully this little sidebar answers any questions anyone else might have had about eggs or mayonnaise in pregnancy.
I still need to see the therapist, but the bottom line is just don’t. If you’re going to make something that uses raw eggs, that’s the only time you really have to think about it. Otherwise, you’re cooking them in the United States, because otherwise we’re just cooking them anyway so even your local, your own eggs that you grow or things like that, if it might not be the choice eggs to make your own mayonnaise from, without taking some risk.
Yeah, so just buy. The store bought mayonnaise, but if you cook them, they’re probably great, so yeah.
All right, sounds good.
Well then, let’s wrap it up. The thinking about OBGYN website will have links to a lot of the things we talked about today, and then we’ll be back in a couple of weeks.