Rescue ACS with PPROM?

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Foreign. If you've been listening to the show, you know that one of my favorite things to talk about is antenatal corticosteroids. It is one of my side projects because antenatal corticosteroids really have been game changing for the world of preterm birth. Not only do they help reduce hyaline membrane disease, a term we no longer use now we call it rds, respiratory distress syndrome. But of course it helps reduce the rates of necrotizing enterocolitis and intraventricular hemorrhage. Now, we've learned a lot about steroids and we're still learning. The last guidance from the college was committee opinion 713 from August of 2017. But things move fast and there's a lot of data here, especially in terms of what is the right dose. Is what we're doing now too much? What is optimization of steroids? Even though the SMFM currently says, at least for research purposes, optimal dose of steroids is giving the first dose with delivery interval occurring within six hours. Yeah, that's fast to up to seven days, Things are changing. We now have evidence that the steroid effect can last as long as 14 days. So in that original committee opinion, August of 2017, which was number 713, it states that rescue steroids can be given if the previous course was given 14 days previously. I know we all learned the seven days. We all like our rescue at seven. The truth is not needed until 14 days. But committee opinion 713 does make that caveat, that little statement that says, hey, look, there are some situations based on the clinical scenario where rescue course steroids can be given as early as seven days. But the original language says within 14 days of last initial course. So intact membranes, everybody gets it. There's some times when rescue course of steroids can be given as long as the first course was given 14 days prior. But the question, and this is where we're going in this episode, what about in patients with preterm pre labor and prolonged ruptured membranes? Now, right now, ACOG's current statement is, hey, we don't have enough information. I don't know you, do you? You could potentially risk infection. I don't know if there's real neonatal benefit. We don't know. But remember that was the stance from August 2017. Man, things move fast. We got a lot of data now. So in this episode we're gonna tackle that question. Are rescue steroids and any better? Do they help reduce neonatal adverse issues any more than a single course? In patients who had ruptured membranes. And what about the potential risks? So this is brand new. We're going to cover this because In May of 2026, just two months ago, a systematic review and meta analysis came out on this very subject. And we're going to tackle this. Look how things move fast, right? 2017, we don't know insufficient data. But now we have a systematic review and meta analysis that helps answer this. And we're not just gonna focus on that. We're actually gonna go back in time a little bit to 2023 and focus on one RCT. That was very well done. And it also is in line with this meta analysis and systematic review findings to a point. I'll explain in a minute. All right. Plus think about this guys. There is this proposed theory, and it's been around for about 30 years, that the little babies in utero that have the presence of preterm, pre labor rupture of membranes, that chronic inflamma and the state of being ruptured triggers a kind of stress response in the child. So the child already makes his own natural booster because he has his own antenatal corticosteroids because of this physiologic stress response in cases of PPROM or triple P rom preterm pre labor, prolonged rupture of membranes. And the real issue is as beneficial as those steroids are for the child, they do function as a potent immunosuppressant in in the mother. So does that potentially put the mother at risk of infection which then has a negative impact, of course, on the child? Remember, we went from insufficient data to now we've got some pretty good data on rescue antenatal corticosteroids after PP R O M or triple P R O M. That's where we're going in this episode. We're going to get to it. Coming up next, we're just trying to fulfill our life calling and our mission. This is Dr. Chapas, OBGYN no Spin podcast. All right, Podcast family, right at the beginning, let's just clarify this. We are not raising the question of whether or not to give steroids initially in patients with PP R O M. That's a no brainer, especially if they're in the non controversial gestational age of 24 to 34 weeks. Please give them steroids. I mean that's the standard. The question at hand is if they remain undelivered and about two weeks later, should you give them a repeat or a rescue or some people call them again a booster dose of steroid at that time. So no one's questioning the initial round of steroids. That's not the question here. If they qualify based on gestational age and the threat of preterm birth, please give them steroids. The question has to do with rescue or repeat courses when they are ruptured. Look, this steroid issue, man, I mean, how fascinating is this? There's so much data on this and authors are questioning things like, hey, is the dose that we're giving too much? There was actually a placenta bench model looking at pharmacokinetics of lower doses and they're like, you know what, we're probably giving way too much. Even the dose may be supraphysiologic. That's why you probably can spread this out until 14 days before you need a rescue course. But as of right now, of course the current doses remain what they are. And of course we've learned that the maximal time to benefit is unclear. While traditionally we said 48 hours for maximal steroid benefit, meaning 48 hours from the first injection or 24 hours from the second of betamethasone, look, we don't know. There's probably good effect as early as six hours from administration. That's according to SMFM's position statement of using steroid time administration to birth interval as a quality metric. Back in 2022, there's some benefit as early as six hours. Now, I'm not trying to confuse anyone, but I am trying to make the case that the data on steroids is rapidly, rapidly changing. So even that opinion from SMFM where optimal dosing was six hours from a first dose to delivery, even that is now considered outdated because the Melamod publication from JAMA Network open just from last year in 2025, this was a very large Canadian retrospective study. It was close to 8,000 newborns, found that, look, there seems to be a reduction in neonatal mortality as early as here it is, guys, two hours after the first dose and then it actually peaks at 12 hours following exposure with the effect lasting for a full 14 days. That was JAMA Network open the very well received melamod study from 2025, even though it was retrospective. So a lot of things changing here. So we went, oh my goodness, it's seven days as a rescue course to now potentially 14 days, 14 days is the better option. And the whole idea of steroid benefit that's taking 48 hours is just not true. There is mortality benefit as early as 2 hours reaching a peak according to 2025 data at early as 12 hours. So all of these things are changing. And where we're going here in this episode is to try to answer the question, are rescue steroids necessary? Is there fetal benefit without risking any kind of fetal or maternal harm with rescue or repeat courses in patients who are ruptured and remain undelivered after the initial course? A lot of things changing here. Okay, now check this out. Look how fast things move. Even the 2022 Cochrane Meta Analysis that looked at repeat course of steroids in intact membranes and did some benefit there. They specifically did not get into the issue of rescue course in pprom. But now we've got this data. All right, so let's start at the very beginning. Let's start out one of the best studies that looked at this in a systematic way, in a controlled way. It was an RCT back in 2009. This was in the gray journal, it was the Garrett et al publication that is G A R I T E, the Garrett et al publication. And it did show that a rescue course significantly reduced neonatal respiratory morbidity. But those were in patients who were not ruptured, by the way. You know, when they gave that rescue course, that rescue course had to be 14 days after the initial course of steroids. See, that 14 days goes out back to 2009. It's nothing new. And is referenced again in Committee Opinion 71 3. So back in 2009, Garrett et al looked at rescue course of steroids and said, yeah, if you wait for two weeks and they're undelivered and the threat of preterm labor, labor is still there and if you give them another dose, yeah, they had help, they had better outcomes compared to a single course. However, one of the exclusion criteria were those who were ruptured. Okay, so like we're not messing with that. I don't know too much theoretical risk here about infection. So we're not going to get into that. So they completely excluded patients with PPROM. So let's leave 2009 and now let's try to get to this answer in 2023. And we're actually gonna look at two studies. I know I said in the intro that we're just gonna do an RCT from it, and I did want that to get the top bill because an RCT is a better design, but there's actually a retrospective study that we're also gonna talk about that same year. Okay, so a retrospective study and an RCT from 2023. And then we get into the meta analysis from two months ago. May of 2026 on whether or not we should get rescue steroids in patients who are ruptured. So first, this retrospective study, kind of disappointing because in this very publication they figured out that in those patients who had an initial course of steroids and then went on to rupture and had a rescue course, or initially were ruptured, got an initial steroid course, remain undelivered, and got a rescue course, they actually had worse outcomes in terms of infection compared to those who were intact and had an initial course of steroids and a repeat rescue course, but they were still intact. So let me just read you these three groups here, and I'm gonna tell you the results very quickly. Remember, retrospective study, but still very nicely done. Group one were those who had intact membranes at initial dosing and then those who had intact membranes at rescue. Group two started intact, but then they had rupture and had rescue core steroids with ruptured membranes. Group three were ruptured all the way through. Okay, so they had PPROM at initial dosing and then PPROM at rescue. Three different groups. Now, this wasn't a big publication. It was just a total of 143 patients. But nonetheless, check this out. Neonatal sepsis, guys, again, that's bad. Neonatal sepsis occurred in 6.8% of patients in group one. Those are the ones who got one course and then rescue and remained intact without being ruptured the entire course, whereas it was 21% in patients with group 2. Remember, those are the ones that were intact at start, then ruptured, then had a rescue course. So we went from 6.8% to 21. Now, in those who were ruptured initially had a course of steroids and then repeated it later and still ruptured, they had a rate of neonatal sepsis of 23.8%. So the point was, according to this publication, the relative risk of neonatal sepsis after a rescue course in patients with pprom in groups 2 and 3 was 3.31. So that's pretty impressive. Remember, it's retrospective, but they gave us some good data here that, unlike the 2017 publication from the college, that is now, again, a little dated, we now know, at least in this retrospective observational study, that a rescue course of corticosteroids in women with PPROM at the time of rescue administration was associated with an increased risk of neonatal sepsis. End quote. Of course, they say larger studies are needed to, you know, to validate this, but they said, look, be careful of rescue steroids in patients who are ruptured. That's good info. That didn't exist when Committee Opinion 713 came out in 2021. Okay, so again, I'm sorry, in 2017. So Committee Opinion 713 was in 2017, this was in 2023. More data. Now let's leave that from 2023 as a retrospective study and let's go to a different study the same year. That is an rct. This is in the Pink journal. This is the Pareco paper. Right. So let me explain this. Now here's what's interesting. Pareco and Garrett is the second author on this, the one that we just discussed. This is now in the Pink journal from May of 2023. Okay, so that's the American Journal of OB, GYN, MFM. The title is Booster Course of Antinetocorticosteroids after Preterm Pre Labor Rupture of Membranes. A double blind randomized trial. Now here they call it boosters. People call a second dose a lot of things, a repeat course, a rescue course, a booster course. But they're all talking about the same thing. Okay, this was very nicely done. It was multicenter, placebo controlled. It was randomized. The inclusion criteria were patients who were ruptured with gestational ages from 24 up to 32 weeks and six days. All right, so 24 up to, say, 33 weeks. Now, the initial course of antenatal corticosteroids here had to be at least seven days before randomization. And then they had a second course of betamethasone for two courses or placebo. And then they figured out what happened. The primary outcome was a composite of neonatal morbidity or death. Alright, so the babies do better. Remember, these patients were all ruptured and had steroids, in this case, at least seven days before. Now watch this. Remember, primary outcome, neonatal morbidity or death. The primary outcome occurred in 64% of patients who had the booster antenatal corticosteroids versus 66% of patients who received the placebo. You're like, what? That's not really a big difference. You're right. You're exactly right. And so that's the catch, is that there was no real benefit to getting a rescue course in these patients who were ruptured. Now, the good news was that chorioamnionitis, postpartum endometritis, or wound infection or proven neonatal sepsis were also not different between the groups. So unlike the publication that was retrospective in 2023, that said, we did see an increase in neonatal sepsis. This publication did not. That's the good news. The not so good news is that the primary outcome wasn't really any different. So they concluded a booster course of antenatal corticosteroids at least seven days after the first antenatal corticosteroid course in patients with preterm pre labor rupture of membranes did not improve neonatal morbidity or any other outcome in this adequately powered, double blind, randomized clinical trial. End quote. The good news, of course, it didn't increase maternal infection either. So you really got no bang for your buck. It really didn't do anything. Guys, we're trying to answer the question here. Let's just go back to the original question. Should we be given antinetocorticosteroids in patients who are ruptured? Since ACOG's committee opinion 713 back in 2017 said we have insufficient data, we don't know. Well, we've got this retrospective study from 2023 and this RCT from 2023 that say it didn't really help the kid. One paper said maybe it's increased risk of neonatal se, the other one didn't. I wish we had something else. We have something else. So that brings us to May of 2026, which is a systematic review and meta analysis in the American Journal of Perinatology. This is the DeCosta publication that is D A C O S T A Again, American Journal of Perinatology from May of 2026. I don't want to belabor this. I just want to tell you the results and then I'm going to tell you what I do or don't do in these cases and then we'll wrap it up. Now if you can't tell, I'm trying to lead you a certain way here, okay? But look how medicine moves fast. Guys, this is exciting. Back in 2017 when ACOG released Committee Opinion 713, which is now outdated like, I don't know, we have insufficient data on what to do with steroids as a rescue course in patients who are ruptured. But now we've covered good data and it gives us better idea of exactly this question. So let me get back to these results when we start wrapping this up. This was a systematic review and meta analysis of six studies with over 2,400 patients. Let me just read you what they found. Sensitivity analysis showed that repeat course of corticosteroids increase the risk of endometritis compared to a Single course, end quote. So that's not good. I mean, we don't want it to go in the opposite direction. We don't want to give anybody an infection. And while that is not good, the relative risk was 1.63. It's respectable. But thankfully it was still under 2. And the confidence interval did touch 1. It was 1.1 to 2.4. So take that for what it is. They also go on to say in the subgroup analysis, there was no overall subgroup difference in the outcomes of respiratory distress syndrome, neonatal sepsis, necrotizing enterocolitis, and interventricular hemorrhage. So the good news is there was no change in the rate of neonatal sepsis. So we didn't cause any babies to get sick, but it really didn't make any difference in the rates of respiratory distress, necrotizing enterocolitis, or interventricular hemorrhage. The bad stuff that we want to improve, there was no differences here. So they concluded because of that little increased relative risk of endometritis. Repeat corticosteroid courses in PPROM may increase maternal infection morbidity without clear neonatal benefit, end quote. Of course, they say we need further well designed randomized trials to prove this and to validate this. Let me say that again, quote. Repeat corticosteroid courses in PPROM may increase maternal infection morbidity without clear neonatal benefit, end quote. And y', all, that's exactly my stance. People have asked throughout the years, hey, you got a patient, she got steroids and now she's ruptured. Should we give her another course? The answer is no, because it really is this theoretical concern of infection, even though the risk may not be, you know, up to 2, but it does point the trend is kind of towards increased risk of infection. It's kind of controversial about neonatal sepsis, but the whole point is it doesn't seem to have any clear neonatal benefit. It doesn't really seem to help in any meaningful way. So, no, I do not give a repeat or a rescue or a booster course of antenatal corticosteroids in patients who are ruptured. Podcast family, as always, we're thankful for you. We're glad you're part of our podcast community. And now that we've done all that, Michael, thank you. So let's take it home. This is Dr. Chapma's OBGYN no Spin podcast.