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What can I get you? I'd like a large coffee. Okay. So hot coffee. Hot coffee. Okay. Room for cream. Totally leave room for cream. Why are you talking like that? Why are you talking like that? Well, going to a coffee shop has become kind of an adventure and kind of an ordeal, hasn't it? I mean, from our beloved baristas who ask you if you want room for coffee. Room for cream. I can't do it to just the ten dollar cup of coffee, y'. All. There's a better way. So I'm thankful that the Strong Coffee Company has partnered with our podcast. That is strong, as in striving to reach our natural greatness. Striving to reach our natural greatness. That is the Strong Coffee Company. And now for our podcast listeners alone, there is a 20 discount for anything that you order online, y'. All. They have Adaptogen coffee gummies. What? So in addition to the regular whole bean variety and the instant mix, from lattes to collagen to L theanine and the gummies, I, I actually, I, I love these things because right before I go into like a long case or something, I knew it was going to be complicated. Man. They actually have nootropic Adaptogen coffee gummies. And now you can buy that with 20 discount only via the link in our show notes. But I always get a kick out of that. Would you like room for cream? Yeah, I like room for cream. You can avoid all that by ordering your coffee online. So, Strong Coffee Company, thank you so much for your partnership or our podcast community. That's the Strong Coffee Company with the link in our show notes. So what are we supposed to do now? Ah, the infamous question that is not a rarity for me to hear throughout the day, either from medical students or residents or some visiting folks that come in and it's a good question. So what are we supposed to do now? That has to do with a result that comes in that we ordered appropriately on this test. We got this test, we're supposed to do that. But then we follow it up and we're like, well, that didn't go the way I thought it would go. Well, what are we supposed to do with that now? Let me explain what that means. In this episode, we're going to talk about the elevated maternal serum alpha fetal protein MSAFP level. But the fetal anatomy scan, the Level 2 survey, is normal. So let me just set this up. That's where we're going. The title is Elevated msafp but normal fetal anatomy. What next? Because that's a good Question. Now, if you're thinking, well, wait a minute, are we still doing msafp? Yeah, you can now MSAFP as a traditional marker either first, historically, as a standalone test for aneuploidy, where a very low multiple of the median, traditionally that was 0.5, was their flag for genetic conditions like trisomies. All that's been replaced, of course, that was integrated then into the, the quad screen. Well, first triple screen, then it went to the quad screen that some people still do for aneuploidy screening. But most have moved away as we've gotten into cell free DNA, knowing of course that it's limited because it only checks for genetic conditions and not fetal body cavity disorders or body cavity defects. And so this is what we're getting here. While our group follows the mainstream norm and traditionally offers everything to the patient, whatever they want to get, either amniocentesis, if they really want to be a diagnostic test receiver, or the cell free DNA option, which of course is very good for 13, 18, 21 and sex chromosome disorders. We get that right. But that only checks, of course, for genetic issues to look for body cavity defects. ACOG says there's two ways to do this. All right. You can either get the routine level 2 anatomy at 18 to 22 weeks, looking at a detailed survey of the baby's body. And we do that. That, that is pretty universal. But then it also says, and this goes back to committee on the, the Obstetrical Committee on Practice bulletins back in 2017, that was practice bulletin187 on neural tube defects says you can either do, just do the normal level 2 and in A, trained, with trained eyes, a normal level 2 is very reassuring. And. Or you could do maternal serum alpha fetal protein, either alone or as a complement. Now that's where we come in. We do that as a complement. So we do a level 2 ultrasound at 18 to 22 weeks. Or should they present for the first time, which is not unusual in our population and like, hey, I'm 32 weeks, I'm here for my first prenatal visit. Well, welcome aboard. Better late than never. Even though it's not the ideal time to do a level two, we'd still do a detailed anatomical survey at that time because we don't want to miss, you know, potentially something that we're not prepared for, like an encephaly or something that, you know, patients could use a good counseling as to what to expect at time of birth. So we do a full anatomy, of course, at 18 to 22 weeks or should they present later? It's just good to look at the body overall at that time. But we also add MSAFP in the correct time frame. Now you can do that anywhere from 15 weeks at the earliest up to 22 weeks. However, the peak time, the best accuracy for body cavity defects seems to be between 18 and 20 weeks and six days. Okay, so AFP, which was one of the first ways. Guys, this goes back all the way to the 70s when alpha fetal protein levels in the serum of pregnant women were found to be a marker of body cavity disorders in the child, traditionally of the neural tube. But, but we also know of course, that some abdominal wall defects can also present with elevated AFP levels. So here's the question. Even though we've had msafp in the 1970s, since the 1970s, and even though its use has changed throughout the history of obstetrics from a standalone test to integration into the triple, then into the quad test, now pretty much replaced by cell free DNA, it still has a role. MSAFP still has a role as either an ancillary and slash or supportive test of the level 2 ultrasound or as a standalone. Some places guys don't have a sonographer, don't have access to a good high resolution ultrasound and they don't get anatomy scans that still exists. Guys, even in the US in some remote parts of the country, or even like in our state, there's remote, remote parts of Texas, man, you gotta do what you gotta do. So, so even though it's limited and not as good as a level 2 ultrasound, MSA of P, between 15 and 22 weeks, peaking accuracy at 18 to 20, still has a role at least as a screen for body cavity defects. Now, we do both, as I mentioned, we get the anatomy scan, that's eyeballs, and then we get the MSA of P. Now here's the question. Well, why would we do that? I mean, don't we just believe the sonographer? Of course. And I gotta tell you, our sonographer Morgan, she is phenomenal. I mean, she's just gifted, you know, sometimes you just get some gifted talent. Man. She's good. I mean, she can find those outflow tracks in that heart. She can find a good, you know, four chamber view, she can follow the outflow tracks, we can look at, at the tangential view of all the major organs, whether sagittal, straight cut, Doppler, she does it all. And she's very good. I trust her eyes. However, we're all human, so it's nice to have a second test that makes sure the MSAFP is also normal. Now, here's the catch. If that MSAFP ordered for body cavity defects is at or above 2.5 moms, that's multiple of the medians, which is abnormal. But the body ultrasound scan is normal. What do we do with that? Now, here's why we also order this. So we order it for two reasons. Number one, it's a backup to the eyeballs because though I trust Morgan universally, as she has earned that, we also do that as a double check for certainty. So number one, we're double checking anything that we're not seeing with a body, with the body cavity scan. And then number two, the second reason is there is place plenty of data, and that's where we're going here. Plenty of data that in patients who have an elevated MSAFP level with a normal fetal anatomy scan, that's a flag. Now, it's a flag for some adverse issues that we're going to discuss here. And it's all part of patient counseling. It's all part of increased awareness. Maybe we bring that patient back a little bit more frequently. We definitely get rid of growth ultrasound, that's for sure. And I'm going to explain why in this episode. So I get it. If you don't do MSAFP for body cavity defects, that's fine. I'm trying to get you to understand the data that it's very reasonable and very conservative to consider that. So if you haven't done that as part of your integrated plan for body cavity defect search, then consider that. Or bring this up at Journal Club. Look at the articles that we're going to put in our show notes. Just take a look at that because it's a good double screen for somebody's eyeballs. And more importantly, it is a flag in that if the multiple of the median is at or more than 2.5 for MSAFP in the maternal serum, but there's still a negative scan between 18 and 22 weeks of the body, something is going on. So we're going to answer these questions. What does that mean? What do we do with that? Why do we do this? Now, as we started off this intro with, we're going to discuss that, we're also going to get into how do we surveil these? We're going to get into that and then we're going to answer, well, where does it come from? If it's not coming from a body cavity disorder or a defect, if it's not coming from the neural tube, where Is it coming from? Does a placenta make this thing? We're going to answer this in this episode. So it's kind of fascinating, it's kind of neat. And we're talking about this because this happened to us just the other day where we had a patient, of course, who had a elevated MSAFP but a normal fetal survey. So the question was, so what are we supposed to do now, exactly? Well, what are we supposed to do now? I'm gonna tell you in this episode. I think I've set it up enough. Let's get to it. Tired of all the spin in women's health education? Yeah, so are we. This is Dr. Chapa's OBGYN no Spin podcast. When did making plans get this complicated? 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So, as I said in the intro, the ACOG says that assessment for congenital malformations can be done either with a detailed fetal ultrasound or msafp, or you can do both as we do it kind of as a double screen. Now, if you're going to do msafp, if you haven't been doing this, it's okay. It's all right. I'm just trying to tell you that maybe there's some value to do this. And just make sure you order the right test. It was about, I don't know, three or four years ago. One of our nurses in our clinic came to me and said, oh, my God, something's wrong. Something's wrong with the baby. I'm like, whoa, what's going on? Relax. What is happening? And she said, my AFP is off. And I'm like, well, do we get the ultrasound? Ultrasound looks great. I'm like, okay, well, let me take a look at the result myself. Well, somebody had Inadvertently checked off alpha fetal protein as a tumor marker. Yeah, don't order that because, yeah, the patient who's pregnant actually has a benign growth inside of her, kind of like a tumor, it's called a child. And so that's going to throw off AFP as a tumor marker. Don't order that. It's got to be AFP for neural tube defect assessment. Okay, so AFP for neural tube defect assessment, that's called a multiple other median. So AFP is a, is a good test in the serum because it detects this protein that goes through the placenta, the maternal blood into the maternal circulation, and ideally, and most traditionally is elevated in cases of neural tube defect. Okay, but it could also signal a body cavity defect of just anywhere. But traditionally it is the neural tubes. You gotta assess that very carefully. So again, if you're just doing level two, nothing wrong with it, that's fine. But what we do, and I think it's the most conservative, as I mentioned in the intro, is that when you combine these two together, if there is an elevated in AFP 2.5 multiples of the median with a normal scan, it could be a marker of things to come and potentially that patient could use some surveillance. Okay, so number one, if you're going to do this, don't order the tumor marker, order the correct test, which is msafp. Now, there are several things we got to keep in mind here. AFP is not new. As I mentioned again in the intro, it goes back all the way in to the 70s. And while it is very reassuring, very reassuring, I mean, the chance that you're missing a significant defect with a normal level 2 ultrasound, especially a good detailed view of the intracranial structures and all the way down to, to the sacrum of the spine of the child, making sure that there's no, you know, defect, either spina bifida or meningomyocele or whatever, the. That actually drops, that is normal. It drops the chance that there's a fetal anomaly in the neural cord to like under 0.5%. I mean, it's just extremely accurate to look at things. However, if ms.afp is elevated, it's coming from somewhere. And that's the catch is where's it coming from? And what does that mean? Okay, now here's the data as we, you know, we've been kind of true to our form here, just telling you what you need to know and then being done with a lot of verbosity, which is very easy for me to do. The short of it is, is that an elevated maternal serum AFP done at the routine time. Guys, that is only done between 18 and 22 weeks. I'm sorry, 15 to 22 weeks. But the peak goal is around 18 to 20 weeks. So 15 to 22, you can't do it before that. It's going to be weird. You can't do it after that. It's uninterpretable. It's only at that slice of that window. Okay, so if you get that an elevated maternal serum alpha fetal protein level, even when a detailed fetal anatomical ultrasound is normal. Here it is. Guys, here's a clinical burl. Here's the no spin part of our podcast. That is a flag that without question is an increased risk for some adverse perinatal outcomes, including preeclampsia, placental abruption, preterm delivery, fetal growth restriction, and even some increase in perinatal mortality. So this is a flag. Okay. Now there's no direct indication just to do surveillance in this in terms of, you know, non stress test or biophysical profiles, but you do surveillance in terms of fetal growth because there is pretty robust data that shows that there's an association with fetal growth restriction. It is recommended to follow this every four to six weeks for growth. Okay. That's why I'm saying there is some value here in getting this. Even though the anatomical survey is going to be ordered. Now, I know what you're saying. I know it well. What am I supposed to do with that? Okay, I can't prevent fdr. No. But for example, if she is not yet taking low dose aspirin, and I'm a big fan of low dose aspirin, you know that almost universally. Almost universally. Because we're getting this still typically around the 20 week mark. There is benefit to start this, of course, under 28. Now the most evidence shows that you can start this pretty darn early, of course, at around 12 weeks with some data saying there's no harm starting in the first trimester, but before that. But in general it's at 12 weeks or beyond up to 28 weeks. So there is still time to jump on board the aspirin train. That's where I'm going for. Because we can make a dent a little bit into preeclampsia, which could then, because of the altered vasculature, be an indirect help to reduce fetal growth restriction. Although we don't use aspirin right now for fetal growth restriction prophylaxis. Right. So my point is there is some value here. So as we tell patients, there is some Good news and there's some not so good news. The good news is that if you have a normal detailed anatomical survey, the risk of major congenital anomalies like open neural tube defects or even again, based on who you read, maybe some ventral wall defects in the is extremely low after a normal high resolution ultrasound. That's the good news. The not so good news is that your body has detected this high level of MSAFP is specifically when it's greater than three multiples of the median, 2.5 is a cutoff or abnormal. But if it's greater than three, then you're really high risk for these issues like preeclampsia, abruption, preterm delivery, and even fgr. So we got to do something about that. So it's a good news and not so good news issue. Now, I've read different stats on the chance of missing a neural tube defect with a normal anatomical scan. And based on who you believe, it's either like less than 0.5. Some say that the chance of missing something with a good trained eyes and getting a good survey is as low as 0.05. I mean like 99.9% sure. Everything looks great. That's very reassuring. So a couple of clinical pearls. Number one, consider MSAFP in addition to level two anatomical survey, but know what to do with that. Number two, if you have a negative anatomical survey, that's phenomenal, phenomenal, phenomenal for reassurance that there's nothing wrong with the neural tube anywhere from 99.5% sure to some say 99% sure. So really darn good. But if the elevated if AAP is elevated in the maternal serum, it's coming from somewhere. And that's where we're going to get into. Where is it coming from? Does a placenta make it. Is it a lab fluke? And you don't have to recheck it, you just leave it alone. Just find it that it's abnormal, only check it once and move away as long as you order in the right time frame, which means that you have to have the correct dates. Okay, so dating has to be assured here. So where is it coming from? We're going to answer that coming up next. You're listening to the OB GYN no Spin podcast Foreign this episode is brought to you by State Farm. Listening to this podcast. Smart move being financially savvy. Smart move. Another smart move having State Farm help you create a competitive price when you choose to bundle home and auto bundling. Just another way to save with the personal price Plan like a good neighbor State Farm is there. Prices are based on rating plans that vary by state. Coverage options are selected by the customer. Availability, amount of discounts, and savings and eligibility vary by state. All right, so as we mentioned before the mini break there that there is data, no question, that AFP is also elevated with ventral body cavity defects like omphalocele gastroschisis. But it doesn't tend to be as elevated as with the neural tube defects. But neural tube gets all the attention, and it should. But AFP is not just specific to that because it can also be elevated with things like omphalocele. So the question is, well, where is this coming from? Where is the extra AFP that's being found in maternal circulation? Where is that coming from? And the short answer is, in my most medical jargon, here it is in. Is that the placenta is janky. All right, the placenta is all janked up, right? The placenta is not good. Why? And it has to do with os. OS oxidative stress. We know that oxidative stress is bad. That messes up the circulation, the vasculature, implantation, even starting very early on in the first trimester. Oxidative stress affects angiogenesis in vasoconstrictors at the placental interface, which is with the myometrum. So this is a placental issue. The reason that maternal serum alpha fetal protein is elevated even in the cases of normal body body cavity evaluation with ultrasound, is that the permeability. Here it is, guys. Short answer is, is that the barrier. That's the placenta is janky. So it allows for a lot more weepage and. And seepage of otherwise AFP that wouldn't. That shouldn't entrance into maternal circulation. It's placenta. Okay, so it's a. It's a sign of. Here it is. Placental dysfunction. So the short answer of what do we do with this now? Is. Well, pay attention to it. It's an abnormality. Don't just brush it aside as a false positive. It absolutely is a false positive to a degree of 0.5 to 0.1, 0.05 error if there's a normal ultrasound of the neural tube. But it's not a false positive in terms of the potential for adverse perinatal outcomes. Does that make sense? So don't ignore it. So what do we do now? You can surveil fetal growth. You can start the patient on aspirin, you can monitor blood pressures. And it's all about patient awareness. All right, so it has to do with oxidative stress that causes this permeability of the placenta that allows leakage from the fetal compartment through the placenta into the maternal circulation. Which is why you get that increase in maternal serum alpha fetal protein above 2.5. And especially worrisome if it's above 3.3 multiples of the median. All to say, this is very well published, where even with placental study after birth atom of delivery, this has been linked to placental infarcts, placental thrombosis, angiomas of the placenta, some abnormal placental villus architecture at the microscopic level, even in the absence of fetal anomalies. So if you have an elevated msafp, it's a good idea to send a placenta off to histology, look at it grossly, just to try to explain what's happening. Now, be very clear, in no means is this a 100% causality or 100% association that that patient is doomed to get those adverse issues. It doesn't mean. So please don't say, well, you're, you're. Trains off the rails, honey. Nothing I can do. There's just. There's no engineer on the front of that train. It says going off the rails. No, no, no, no. This is just relative risk. If you have an elevated maternal serum alpha fetal protein with a normal fetal survey, your relative risk of having preeclampsia, your relative risk of having fetal growth restriction, of having oligo hyramnias, of having a preterm birth, anything that goes with a janky placenta, those are pretty much going to be elevated. But it doesn't mean that is 100%. So what do we do? We're going to put you in fetal growth surveillance. We're going to monitor your blood pressure. If you're not yet on low dose aspirin and don't have a contraindication, consider starting that under 28 weeks. That's the indication here. Now, again, there's no indication for endopartum fetal surveillance in terms of NST or biophysical profile, unless you find something like fgr, which you should track, of course, with umbilical artery dopplers and continued traditional antepartone fetal surveillance. But. So while there's not an indication for BPPs or NSTs alone, it is an indication to track fetal growth. All right, so I found this interesting. This is what we're doing in our patient who had an elevated maternal serum alpha fetal protein. If I remember right, I think her multiple of the median was like 2.8 close to 2.9, close to that 3 cutoff. But her anatomical scan is normal. So once again, I told her resident, that's a damn good topic. We're gonna put that together as an episode. And it's relatively brief. Don't ignore it. Follow growth. And if you're not getting msafp, that's all right. It's all right. It's so good. It's okay. Just do a good anatomical survey. We have chosen to do that because we want to get as much information as possible that potentially. And here's the catch. Is actionable, as we've already discussed. So elevated msafp, but normal fetal anatomy. What next? Well, we just finished and wrapped that up in this episode. Podcast family, as always, we're thankful for you. We're glad you're part of our podcast community. Thank you for all of your support and your encouragement from the US and abroad. We appreciate you. Now that we've done all that, we're gonna let Michael take us home. Podcast family, we're thankful for all the support that you've given us throughout the years. This has been the OBGYN no Spin podcast. We'll see you on the next episode.