D (17:43)
So now that we've done the review from ACOG, let's get into this new publication from AJOG, May of 2026. So very simple. This is not like a systematic review meta analysis of RCTs. They used prospective studies and retrospective cohorts. They threw out case reports, case series. There was just prospective and retrospective. And these were all reports that stated Patients had these weird genome wide nips test that were proven to be false positive because the confirmation fetal test of whatever variety said it's not coming from the kid. Okay, Meaning it's some kind of focal placental mosaism that typically comes from like a unipaternal dysomy or just during the placenta formation kind of splits off and it does weird genetic stuff. So placental mosaism focally is usually to blame for this issue. Right? Genome wide non invasive result that the kid doesn't have. Now if it's a symbol. Symbol, simple genome wide non invasive result like trisomy 6, 16, 4 or 22. Notice these are rare, that's why they're called rats. Rare autosomal trisomies. And it's not coming from the kid. The thought is without a placental biopsy, there's a part of the placenta that's kind of jank. And if the placenta is kind of jank genetically, its function is going to be kind of jank. And. And that is the catch. Don't just ignore it as a false positive. This false positive can be linked to some issues and I'm going to tell you what those are here very quickly in just a minute. Now that's a simple genome wide result. If it is a complex result from cell free DNA, you're like whoa, there's like three things wrong with this and it's really weird. But the kids looks great sonographically. You did an amnio and it's normal. That raises the risk that that aberrant DNA is coming from a malignancy. Now let me just tell you this right off the bat. It's not 100%, but in this review it was about 41%. 41% of those with complex NIPS results that were discordant were harboring some kind of maternal malignancy. Again, how terrifying is that? They just wanted to know if their kid was fine and you end up with a potential malignant suspicion. Okay, it is rare. Let me be very clear. Cancer during pregnancy is like one in a thousand. But if your cell free DNA finds a aberrant complex result, the probability goes up anywhere from 300 to 400 fold. Some say 200, some say 500. The point is several hundred fold higher. And this publication found that the pro. The pooled probability was 0.41, meaning 41% higher than the general population. Don't ignore multiple weird stuff. Call your friendly geneticist, call your friendly neighborhood MFM and go. I heard on the podcast this could be Jank, I need help. That's why you have a consultant. Okay, but if it's a single genome wide variation, yes, those are linked to some real adverse issues. Mainly as you would think, things with the JANK placenta fetal growth restriction, even though they call it IUGR here, we haven't called that in a long time. But fgr, sga, preterm birth and they did try to look for stillbirth, but it was really hard to calculate that because thankfully the overall numbers of stillbirth was still overall low. But it still seemed to have a pooled prevalence higher when the placenta was janked over the general population. But it's hard to give it a true number. Anywhere from like 16 to 20% higher risk above the general population though the absolute number, hear me, the absolute number is still very low. Now before people freak out with that, because that is some scary stuff, guys, remember these are extremely rare findings and the highest risk for the worst outcome, which is stillbirth, was tied to a discordant genome wide finding of trisomy number nine. Weird, right? These aren't again, these aren't the common things. So trisomy 9 that had a high prevalence of like 0.24, meaning 24% higher. Again super rare and not the typical findings. Also trisomy 16 had the highest rate for issues overall. So these are not normal. These again, these are the weird things. And the most common discordant genome wide abnormalities were 6, 16, number 22, this chromosome number 9 that had the highest pooled prevalence for stillbirth. And even then it was at 24% but again super rare, also tries to be 15. So these are odd ones. Just to be clear, these are not ones that you should be finding like on a regular basis if you do need to fire whoever's doing your results and or get different patient population because this is really odd, right? So these genome wide discordant results are not common, I want to be very clear, are not common. And the good news for the child is that 80% of these are false positive. That's the good news. It's not coming from the kid, it's coming from a focal placental mosaism. The not so good news is that a third, and this is the end, guys, we're closing this up. Just over a third of this, actually like 35% in this systematic review and meta analysis can be linked to some adverse perinatal outcome. And so it's a good idea to at least do rate of growth ultrasounds, give patient education. I Don't think this requires surveillance because who knows what we're surveilling, but just pay attention. If the placenta is jacked, the child will tell you. With altered fetal growth, that's the biggest issue. Or fluid abnormalities, which you can find again on your rate of growth. Ultrasounds, not necessarily necessary to do antepartum fetal surveillance. I think that's overkill. The point is, don't ignore the weird stuff. These are rare. These are rare. I want to be clear. Rats, rare autosomal trisomies that are discordant on cell free DNA are not common and 80% are false positive. But they can be linked to a 35% rate of some adverse perinatal issues, mainly fetal growth, preeclampsia, preeclampsia with severe features, preterm birth, and maybe, maybe stillbirth. If it's the weird ones, like 9 or 16. But those are very, very unusual. Podcast family, we have learned so much about cell free DNA. And now in May of 2026, this just reminds us that if you find something weird and it's got multiple weird things, it may be coming from mom. If it's a single genome discrepancy, meaning a weird trisomy, science says that that pregnancy may be at risk. About a 35% chance of it, or 35 of those cases, 35% of those cases with some altered fetal growth or placental issues that should be monitored. So don't ignore a discordant cell free DNA result.
