Can Oral Probiotics Reduce recurrent sPTB?

0:00Viscally responsible, financial geniuses, monetary magicians. These are things people say about drivers who switch their car insurance to progressive and save hundreds. Because progressive offers discounts for paying in full, owning a home, and more, plus you can count on their great customer service to help when you need it so your dollar goes a long way. Visit progressive.com to see if you could save on car insurance. This podcast is sponsored by Talkspace. Last year I went through many different life changes. I needed to take a pause and examine how I was feeling and the inside to better show up for the ones who need me to be my best version of myself. When you're navigating life's changes, Talkspace can help. Talkspace is the number one rated online therapy, bringing you professional support from licensed therapists and psychiatry providers that you can access anytime, anywhere.

1:00Living a busy life, navigating a long distance relationship, becoming a first step father, Talkspace made all of those journeys possible. I could speak with my therapist in the office, I could speak with my therapist in the comfort of my home, I was never alone. Talkspace works with most major insurers and most insured members have a zero dollar copay, no insurance, no problem. Now get $80 off your first month with promo code space80 when you go to Talkspace.com. Match with a licensed therapist today at Talkspace.com. Save $80 with code space80 at Talkspace.com. Do the war in my stomach, between good bacteria and bad bacteria, and I'm sure you've heard wars cost money, you know, like in my good bacteria cost a hundred bucks of bottle.

2:06But here's a good news, like I read the bottle, each pill on the bottle contains 360 billion colony forming units. So per colony, very affordable, I'm getting a deal, I'm going to be, if you count the number of colony forming units per pill, it's a good deal for the wicked high cash that people pay for these, you know, life colony probiotics and I just think he's clever. It's true. I love that that there's a war in my stomach between the good and the bad bacteria. And the truth is, that's actually medically accurate. I mean, 70% of all of our immune system and or the origin of its function is in the GI tract. Guys, we don't have to debate the fact that there's a link between gut health and overall health, overall inflammation, even some mental aspects and mood disorders.

3:06I'm not saying that depression is all caused by your gut, but there's definitely some association between gut health and overall health, including some influences on mood and mental health aspects. Now, we've covered probiotics stuff on this show in the past, mainly regarding bacterial vaginosis and the difference between vaginal application and oral use of probiotic agents. And you got to go back to the archives because I know that we covered that not too long ago, but anyway, I don't want to divert into that, but I was at a store and I saw these university town and there's these obvious college students, these young women and they're hovering in the kind of whisper into each other and there's something like, here's the word, Jaina, as I'm walking by, oh my god, don't stop, just keep going, just kind of couldn't help it. I'm sorry, I'm not trying to hit on you because my wife would kill me. But if you're talking about probiotics, let me give you some info.

4:08And they were super thankful. They thought it was kind of funny, but nonetheless, I've pointed them in the right direction. All to say, probiotics is kind of a thing and it's a very popular thing. And some of that has to do with marketing, right? They've been marketed to be the end all and be all for our health. And if you take probiotics, you'll never get sick. Well, that's kind of a stretch. I made that up. The point is, yes, sicknesses, it still do happen, but probiotics and gut health are a big deal. That's all about that. However, however, when it comes to the area of obstetrics, which of course is my little comfort zone, my little home, it gets kind of weird and it gets a little gray and we're going to cover this. So maybe very clear right off the bat. Nobody recommends, oh, hey, you're entering prenatal care zone because you're prebiotic or you're probiotic. That's not a general recommendation. However, if somebody asks you as a patient, hey, I take probiotics, is that okay during pregnancy, you need to be armed with the data for that, especially if they have a high

5:13risk factor like previous preterm birth. So here's where I'm going. On February the 19th, 2026, a new publication out of Japan was just accepted for print and hasn't even come out yet officially. It's an e-pub, right? It's accepted ahead of print. Now, this took a look at 31 hospitals, so there's 31 different sites, it's multi-central, but it was single arm non-blinded. Thankfully, it was prospective, but you see the catches here, guys, right? So right off the bat, even in its description, single arm, wait a minute, there's no control, that's kind of a flag. It's non-blinded, that's another flag, but it is prospective and multi-spender. All right, so it's got some kinks to it, it's got some limitations, right in its design, but nonetheless, what were they trying to do? Well, out of Japan, they were looking to see if women with a history of preterm birth, so these are all high risk women who took oral antibiotics of the specific strain, which

6:14we'll get into here in a minute, if that could reduce the risk of preterm birth as a recurrent factor. Fascinating, isn't it? Now, you think, well, how would probiotics even help that? There is some data that good bacteria can help with the placental uterine interface and the modulation of the inflammatory immune cells there, it is a thing. So this is a fascinating study that needs a more study, so I just want to put this out here. I am not advocating for patients with previous preterm births, they go knock themselves out and every day start popping in the bacteria, okay? I'm not. If a patient asks, we need to be armed with data, not opinion, data to say, look, if you're interested, here's a pros, cons, and unknowns of this. The good news is that nowhere in the data has it's shown that taking probiotics, either alone or with prebiotics, in other words, is a food that feeds probiotics, which is basically

7:18prebiotics and nothing more than non digestible plant-based fiber, no study has shown that that leads to some kind of bacterial sepsis or actual harm in pregnancy. Except, okay, so here's the caveat, I'm going to get into this after the intro, which is the intro, except maybe possibly, notice those words that are those qualifiers, maybe possibly an association with an increased risk and preeclampsia, but even that is debated because it may have to do with when the actual probiotic was taken, okay? Sorry, I kind of lost my word there, so if you can't tell, if you notice my, I don't know, maybe you've never heard of the show before, but this is not my normal voice. I have, once again, caught some kind of allergy-slash viral syndrome, whatever, so I'm doing this, I've got two cups of coffee, could you cup some front of me? One is my rise coffee, because I'm trying to get a little caffeine to do something here, then the other, I've got my, my hot, ferroflu, talinol, slash, liquid, lemon, medicine,

8:24thing, whatever, so yeah, I'm going back and forth between those, it's weird, it doesn't taste good, but I'm trying to do what I've got to do, so yes, I have two different drinks in front of me based on what the spirit leads me to, I either take a sip of my rise or of my ferroflu not, a sponsor. So what, where am I, what am I doing Michael, huh, oh yeah, so there's one study, there's one study that shows that probiotics potentially may increase preterm labor risk, that was an umbrella meta-analysis, I'm getting to that minute, just from last year guys, 2025, but that's got some limitations too. So short of it is, if a patient wants to take a probiotic and they didn't get it from some guy off the street corner and seems to be legit, okay, we're going to give you the data for that, I'm going to give you the good, the bad, and the unknown as it relates to a brand new study, not yet out officially in print, from the Grey Journal, from Japan,

9:24about recurrent preterm birth and oral, non-vaginal, oral probiotics, my goodness, that's some mouthful. I think I've set it up enough, let me take a double swish of my rise coffee and then write their flu, we'll be right back. Podcast family, I'm happy to share information from one of our corporate sponsors, Perspective Medical, in a C-section every second counts, especially when managing postpartum hemorrhage, but traditional surgical draping often hides the very signs that we need to see, concealed bleeding around or under the patient, introducing the OB-GYN, Physician Designed, Hemorrhage View C-section Drape, it's designed to provide clear and direct visualization of the patient to allow assessment of any concealed bleeding. Now, you can recognize hemorrhage earlier and monitor bleeding in real time without compromising the sterile field, whether you're placing the uterine balloon or administering uterotonics or assisting in the second stage C-section, you now have clear visualization

10:29you need to act fast, so let's be proactive, not reactive, in the recognition and management of hemorrhage, visit PerspectiveMedical.org to learn more about the hemorrhage view C-section drape or to request a trial option. Oh my goodness, I'm going to use that next time I'm arguing with somebody, hey man, look, your gut must be off, just take a probiotic, oh that is so stupid. I don't even know what that clip was, some women arguing, I don't know, was that the

11:29housewives or something that show who knows, well not the sponsor, okay, so probiotics and obstetrics, there's probiotic data for pretty much everything, mental mood disorders, of course inflammation, that's a big one, heart health, yes overall immunity, yes, autoimmune issues, yes, of gynecological things like BV, yes, again we've covered that, the question is for our particular home in obstetrics, if you see a patient and they say hey, I'm starting prenatal care, I take my daily probiotic, is it okay, this is to arm ourselves with that, okay, because we're surrounded by all of these commercials about probiotics versus prebiotics and or both, so very quickly just as the recap probiotics typically are live colonies, they are live bacteria that is supposed to help our microbiome reset itself, okay, now the best

12:29are the kind that are real cultures that you have to keep refrigerated versus the freeze-dried capsules that you kind of get off the shelf where the bacteria are supposed to reactivate kind of in the body, you know, who knows if that's true or not, I'm not trying to knock off the freeze-dried probiotics, but there's definitely data that the better quality seem to be the ones you have to keep refrigerated like a lab experiment on the second shelf of your refrigerator, okay, so probiotics, even in neonatology, guys, I'm getting, let me get away from parinatology with the obstetrical world, but in neonatology, there's data that when tiny little, you know, sick babies get probiotics administered to them, it actually reduces some morbidity, like, energizing intercalitis, it can help reduce mortality, and it depends on the obviously on the kind of strain of probiotics that is used, but there's no question that out of the neonatology literature

13:31appropriately given probiotics, typically a multiple-strain probiotics, have some kind of benefit there to help the child establish his own immunity and microbiome. I'm not making that up, guys, that's a big thing, because I found that fascinating when I read that starting about five years ago. However, probiotics given to pregnant women, that's a little trickier issue. Then there's the whole debate versus should be vaginal, that's a first vaginal pass, or oral. Obviously, vaginal probiotics offer some theoretical advantages by directly restoring lactobacilli in the site, closest to the uterus, and where the child will obviously transverse. There's data for that. There has been a randomized trial in women with vaginal dysbiosis, otherwise known as BV, that found that vaginal lactobacilli is specifically a specific one called lactobacillus, KC, aromisus, can significantly increase gestational age at delivery and help prevent little birth

14:35weight. What? I mean, it's out there. Now, no one's going to promote this. This is why this is, we definitely need a lot more data, and remember that things placed vaginally outside of some minimal absorption into the bloodstream. It's sometimes, you know, thought to be better than entering into the GI tract for a variety of different reasons when it comes to obstetrics. So there is data that oral probiotics may not work as well as vaginal probiotics, but we need a lot more data. But, but if you're at somebody asked you, is there any data for vaginal probiotics and obstetrics? Yeah, there is. And it was actually a randomized trial, but, but we need much more data before this is advocated for everybody. Remember, those patients had vaginal dysbiosis. That's the medical term that the sciencey term for BV, okay? So we do have some data. The problem is the study populations that have looked at this have been very heterogeneous. Some have included

15:36low-risk populations. Very few have just high-risk populations like this study that we're going to cover. These patients had a previous pre-term birth. And then some have kind of a mixture. And then there's the big question here is what kind of probiotic is being used? You can just do a study, say, and call it probiotics because there's different strains. There's different colony counts. Some are mixed strains. Some are a single bacteria. Some are live cultures that have to be kept refrigerated. Some are grease-ride. Freeze-ride, you see the difference here when we try to link all studies in under one umbrella of probiotics. There's just way too much there to try to figure out. Now, is there some data where it could be that it could be beneficial? And the answer is yes. There's actually a very large Norwegian cohort study that had over 70,000 women that found that probiotics in milk, okay? When taken early in pregnancy can be associated with reduced

16:37risks of pre-term birth. Now, the odds ratio for that study, again out of Norway, was 0.79. So it wasn't like half, but I'll take any reduction. That's fine. And the conference interval was just under one. It was 0.6 up to 0.97. So it got close to one, but it didn't include it. Meaning maybe there's something there. This was published back in 2018 in BMJ Open, okay? But here's the catch. This was not an RCT. It was a population-based prospective cohort study. So that's one of the catches. Again, there is data, but just because you have data doesn't mean it's high quality data, but it's reassuring that this one showed, yeah, for prevention of pre-term birth when taken early, but maybe you could do something. Now, now, here's the catch. Probiotic milk intake in late pregnancy. Okay, so here's listen to this guys. This is clinical pearl. Probiotic milk intake, according to this Norwegian study, again, BMJ Open, 2018,

17:41taken in late pregnancy was associated with lower preeclampsia risk, but when it was done early on, couldn't really tell what happened. It was a very small benefit, okay? So perhaps it has to do with the initiation of the probiotic and its overall outcome. So again, according to this Norway study, when probiotic milk was taken in early pregnancy, it helped reduce pre-term birth, but it wasn't an RCT. And when it was taken late in pregnancy, it showed lower preeclampsia risk. So this is why I guess confusing. So you've got this very large population cohort study from Norway showing it has to do with timing. And if you take it late in pregnancy, preeclampsia can go down. But if you just throw in all the data, if you put in probiotic and preeclampsia risk, regardless of timing, then things get great. Because here it is, guys, a Cochrane systematic

18:45review in 2021 showed that oral probiotics, yes, could potentially be helpful in sugar control, and therefore in preventing gestational diabetes. But it found an increased risk of preeclampsia. Thankfully, the relative risk was under two, but it was 1.85. So it was above one, but not quite two. And the confidence interval was 1.04. So it did touch one up to 3.29. So they said, I don't know, maybe maybe something of concern there. Remember, that was Cochrane 2021, and that was again kind of reinforced by a separate 2025 Umbrella meta analysis that said that probiotics, yes, possibly could increase preeclampsia odds, but they found a lower relative risk as opposed to the first Cochrane review. So Cochrane review 2021 found an increased risk of preeclampsia with a relative risk of 1.85. But the 2025 Umbrella meta analysis found a relative risk of 1.23. So confusing. You see that? So this, this is why things get very, very gray. So

19:55what's my take home? It may be can help when you take it in late pregnancy, according to the Norwegian study, but if it's taken without regard to gestational age, potentially could lead to like a 12 percent increase in preeclampsia risk. Now, let me pause here for a minute. So it is kind of unknown. I mean, to say very clearly, it's kind of contradictory whether oral probiotics increase preeclampsia or not. There is data that it does, but the percent is kind of small. This is why if we're talking about preeclampsia and you listen to my aspirin podcast and even the one with my friend Alex who had this, I think it was called Alex's input about aspirin and preeclampsia risk. I'm all for universal. Listen to our risk stratified. Just give everybody aspirin whether it's 81 milligrams or like me, I favor the 162 milligrams and you can get a kind of a handle a suppression effect on baseline risk of preeclampsia in the general population as well as those that are at higher risk. So just throwing that out there. So there is some gray stuff guys, gray stuff about oral

21:02probiotics and preeclampsia. However, the good news is is that the variety of studies, both as single studies and multiple systematic reviews and analyses, haven't really shown any excess harm outside of that small little blip of uncertainty for preeclampsia, regarding other prenatal issues. The question is that we're supposed to answer and we're about to do here and we're going to do this quick now because I just want to speak this up. Is what do we do with this with preterm birth? Now, it'll be very clear. Preterm birth, I'm not talking as an incident, we're talking about recurrent. So it's really happened to a patient. She says, hey, we'll probiotics because of my gut health. Can that help reduce the risk of recurrent preterm birth? Well, right now there's what's existing in the data and then there's brand new data. Right now, what's existing in the data is that that doesn't seem to be the case. So we don't have high quality evidence from well-designed RCTs that oral antibiotics or vaginal for that reason cause a significant reduction in

22:11preterm birth. We have population based studies, we have retrospective studies, we have some based on questionnaires, which obviously have issues, but we don't have a lot of high evidence that oral or vaginal probiotics can significantly, that's a catch, significantly reduce preterm birth. This is why guys, this is why I found this new publication out of Japan in the gray journal very intriguing because it at least opens it door to discussion. So and it shuts down the naysayers like, that's not going to help. Wait a minute, just because you don't know about it or hasn't been studied yet, doesn't mean it doesn't help. This study had some beneficial outcomes. It actually worked spoiler, but it was single arm non-blinded, non-randomized. So there's some issues, okay? But I think it's a fascinating discussion. Now before we get into this study, let me just tell you that they used clostridium bacteria as their probiotic of choice here. Now that freaks people out

23:17because we're so used to hearing things like C-diff, clostridium perfringes, clostridium tetanide, all of which nobody wants, right? You don't want to get C-diff, you don't want to get C-perfringes, that's gas gangrene, you don't want to get clostridium tetanide, that's tetanus. So clostridium kind of freaks people out. However, yet another clinical pearl, don't forget that clostridium species are varied and they are a big part of the normal gastrointestinal flora in healthy individuals across all age groups and whether you're a man or a woman. So clostridium lives in us. It's just certain players, certain cousins of the clostridium family that are really bad, but some are actually very helpful. So I found that so, so interesting. So this single-arm prospect of not randomized study used clostridium species, the good kind, specifically clostridium butericum, yeah, I'm not saying,

24:19I should say that again, clostridium butericum, as their main probiotic strain, even though there was others included in there, okay? So that's what we're going, that's just set up. I just want to let you know what exists out there. Is it harmful to take a probiotic? Probably not. It's a little gray on preeclampsia thing but maybe it has to do with when you take it with the Norwegian study saying maybe could reduce preeclampsia if you take it late in pregnancy and it could maybe increase the stational age in other words, reduce pre-term birth if you take it early in pregnancy. I mean, wow, I mean, you see how confusing this is? That leads us to Japan. Prevention of recurrence spontaneous pre-term birth using probiotics results from a prospective single-arm multi-center trial. Now I love that the authors put that into their titles. So it's not giving off any false errors, right? So not in RCT. It doesn't have a control group. So again, just take it for what it is.

25:21This does have some issues but it needs to open up the door to this discussion. So here's what they did. Again, using a chief strain of clostridium butericum, they wanted to see if the use of oral probiotics with that strain help prevent recurrent spontaneous pre-term birth in a subsequent pregnancy. No problem, right? So this spanned 2021 to 2024 as the year range. This included pregnant women that were between 18 and 43 years of age with a history of spontaneous pre-term birth and then they were given oral probiotics and say take it as early as 10 to 14 weeks and then go all the way to 36 weeks and six days which is the end of pre-term labor spectrum. Okay, so we're trying to get to them to get to 37 and zero. The primary endpoint was a rate of recurrence spontaneous pre-term birth under 37 weeks compared to the historical rate of

26:26pre-term birth in Japan's national database which was 22.3%. Let me stop there for a minute. That's high guys. That's pretty high. So according to the authors, the historical rate in Japan's national perinatal database for pre-term birth is 22.3%. I don't know if you knew that, just throwing that out there. The short of it is they also looked at the rate of spontaneous pre-term birth before 34 weeks and some neonatal outcomes. So I just want to do this very quickly. Remember, there's got issues at a rate of limitations and I'm not advocating this for everybody because we definitely need better trials which is what these authors say as they should. But the short of it is it was kind of impressive. Short answer is yeah, it did something. It kind of worked. So among 343 enrolled patients, remember not an RCT, right? 343 said I'll play along 315 so that was 92% of the actual cohort actually went into the analysis. So very quickly,

27:32the recurrence rate of spontaneous pre-term birth under 37 weeks was 14.9% remember the baselines was 22. So this was 14.9% which is an obvious improvement compared to the historical control. Now the secondary endpoint showed that the rate of spontaneous pre-term birth before 34 weeks was 3.5%. Wow. So yeah, it seems to be going in the right direction. Now they also looked at patients whose pre-term birth was at an extreme pre-term EGA. Remember, that's defined as less than 28 weeks among those patients with a history of extreme pre-term delivery again under 28 weeks. The rate of recurrence spontaneous pre-term birth that was extremely early again less than 28 was 1.5%. No stillbirth occurred which is good. There was no serious adverse events. There was no real

28:34complications or side effects from taking these probiotics. So the authors are like, oh, maybe this thing works. So drastic improvement compared to a historical control benchmark, it's, I'm like, if you just read this, you're like, I'm in. However, however, with the limitations we've already discussed, plus, remember, this was from 21 up to about 24. And there was no real obstetrical change during that time of management, but they say, I don't know. I mean, we don't change the way that we took care of patients at that time, but we can't account for some clinician differences in care, some protocol changes for obstetrics that got us to a lower number, but just taken by itself without any kind of univariate or multivariate analysis, it seems intriguing. This was eye-opening enough for the editors of the gray journal to go, yeah, we'll take it. Remember, this is gray, not the pink journal, the gray journal. I would have said, man, you need to do some at least a multivariable or univariable analysis. I don't know. It's got no

29:38control group. Go back to work on it, but it was accepted and it went into print. So it'll be out officially later on. This is just ahead of print, but yes, in this non-controlled single arm non-blinded study, those are all the limitations, or probiotics with clostridium, specific strain of clostridium, actually had wonderful reduction in not just overall preterm birth, but extreme early preterm birth under 28 weeks. Are we ready for this to be mainstream? No. Our major professional society is going to adopt this? No. But if a patient asks you, not for you necessarily to promote, but if a patient asks you, what is the data for this, you go, well, we know in a moment to get sepsis, we know it can possibly help reduce gestational diabetes or help control gestational diabetes. Those are good. Not real sure if it helps with preterm birth, but maybe depends on which strain you take. And the risk of preeclampsia is gray, but maybe to take it later on and not early on, then maybe it can help. Well, some said you say it

30:43can hurt slightly increased rate to 12%. Fascinating. Fascinating that these authors said, well, let's try probiotics. Progesterone kind of went out the door. I am progesterone kind of went out the window. There's still a place for vaginal progesterone, and I'm not going to get into that now. We've covered that many times on the show for prevention of recurrent preterm birth. But my goodness in 2026, I mean, this is where we're at. We're looking at probiotics for preterm birth because nothing else has really done what it's supposed to do. And it's fascinating. My our second child is the product of I am progesterone, 25, 250 milligrams of 17 hydroxyprogesterone, weekly injections. We did those. And then the data was like, well, never mind. Actually, we can't replicate that. Probably is not that big of a deal. So that's gone. But again, there is still a place for vaginal progesterone in the select patient based on cervical length. And even that is

31:45controversial. If you want to go and listen to all of that data, go back into our archive and you can find that. So in brief, we have covered a brand new, not yet released publication from the gray journal, which is prevention of recurrent spontaneous preterm birth using probiotics results from a prospective single arm multi center trial. Is that fascinating or what? So podcast family, I am going to leave you now because I've now consumed all of my rice coffee and my other little cup of dairy flu is nice and cold. Maybe I'll go get some probiotics. What about that? All right. Let's just stop there. Podcast family as always. We're thankful for you. We're glad you're part of our podcast community. Oh, geez, Michael. I only have one nostril. I feel terrible. All right. Now that we've done all that, let's take it home. This is Dr. Chappas, OB-GYN, clinical pearls, no spin podcast.