Perinatologist and medical geneticist Mary E. Norton, MD, discusses the value – and clarifies the limitations – of fetal ultrasound as early as 11 weeks. Illustrating her talk with both normal and abnormal images, she explains which structures are assessed, which defects may be detected and how this knowledge benefits patients. Includes a list of indications for first trimester ultrasound.
Refer to Fetal Treatment Center welcome. My name is Mary Norton and I'm a professor of O. B. G. Y. N. And reproductive sciences at UCSF. My work involves primarily prenatal diagnosis in one of the exciting new areas that we are offering to patients is first trimester an atomic evaluation at 11 to 14 weeks of pregnancy. And that is what I'm going to talk about through this presentation. Here are my disclosures. So first time mr prenatal screening and diagnosis are both being done much earlier in pregnancy. And again ultrasound every generation of ultrasound machines every year get far better and we can see much more detail at all gestational ages But we can see really well at 11-14 weeks. So this is the gestational age when we do a nuclear translucency ultrasound and it is now apparent that much of the fetal anatomy. We can actually see pretty well even at that early gestational age. And obviously for many patients there are great benefits to earlier reassurance in most people when the findings are normal or making a diagnosis if there is a problem, we can provide that information to the patient much earlier in the pregnancy. So one thing about first trimester anatomy, you know again, ultrasound is better and we can see much more detail of the fetus early on. But developmentally there are a lot of things changing at that gestational age and it is important to be aware of what the findings are and what kinds of things might be false positives or um findings that may not be may not be significant. And likewise things that you really just can't diagnose at these earlier earlier gestational ages. So performing these ultrasounds requires good equipment to be able to see the feet as well. Also requires an understanding of normal development and I'll go into that a little bit during this talk. So before about 10 weeks of gestation, when you have just a little embryo, you can't see very much of the fetal anatomy, although you can start to make out some structures. So as early as seven weeks you can see a separate head and the trunk or the body of the fetus By eight weeks. You can make out the core oid plexus By nine weeks. You can see the cerebral hemispheres and that there's a midline to the brain. You can see herniation of the mid gut where the intestines are approaching into the umbilical cord. And usually you can see a stomach by about 10 weeks of of gestation by at 11 to 14 weeks. Again, this is a time when the new cool translucency ultrasound is typically done. So we see lots of patients at this gestational age and many ultra sonography furs and ultra sinologists um now are routinely looking at the fetal an atomic structures and as in the second trimester when we have protocols for a systematic approach and the an atomic structures. We should be looking at. There are now many protocols describing the first trimester fetal anatomy as well. And again, awareness of the normal development is really important. And another thing to bear in mind is that there are many severe fetal anomalies that are not compatible with survival. So we are more likely to see those earlier in gestation than you are later in pregnancy or at terms. So there are some findings that are lethal. These pregnancies often will spontaneously Aboard. And so we see many more of these severe anomalies. Again, things that are unlikely to be seen um at 20 weeks of gestation or certainly at at term and I'll talk a little bit again, give some examples of those. So the International Society of Ultrasound in O. B. G. Y. N. Or S. Wog has a Um practice guideline for first trimester, an atomic ultrasound that was published in 2013. And then in 2019, a group of American organizations, the American Institute of Ultrasound in Medicine ACOG, the Society for maternal fetal Medicine, the perinatal Quality Foundation in a couple of other groups all got together and collaborated on a practice parameter or a guideline for what should be evaluated when doing a first trimester, an atomic ultrasound. Um And again as in the second trimester, having this organized protocol is really important to making sure that one looks at all the critical structures and thinks about what you should be able to see to assure that that structure is developing normal for the gestational age. So again we look at all the organ systems, the head, the neck, the face, the spine etcetera and look for key findings to assure that development is normal for the gestational age. And um these images just kind of show the basic things that we look at. You want to look at the head and see that there's a cranium and a midline structure. This is the profile here. You can see the nice cute little nose and the new cool translucency, the spine, the four chamber heart. The this is the umbilical cord insertion and then actually the extremities are really easily seen at this gestational gestational age. So we have a organ systems and the structures that we want to see within each within each organ system. The central nervous system is one organ system that is continuing to change and evolve over the course of even the first couple of years of life. So there are some structures that have not developed at the end of the first trimester and that we will not be able to diagnose abnormalities or assure that they are normal in this 11 to 14 week time timeframe. So the corpus callosum, for example, doesn't form completely until around 20 weeks of gestation. The cerebellum verma's is still incomplete until about 22 weeks of gestation. So those abnormalities in those organs, we generally cannot diagnose until later in pregnancy. Spina bifida is a relatively common birth defect that's important and spina bifida findings. I will talk about later on in the talk but they are subtle. So spina bifida is not reliably diagnosed um at the 11 to 14 week ultrasound Just to talk a little bit more about the brain. On the left side. These are normal images of the 12 or 13 week fetus. And you can see here there is a fair amount of fluid in front of the core oid plexus. This is normal for this gestational age. And here's the other thing we want to see. This is a cross section through the brain here. You can see the white cranium and here is the midline fox and this is the um Corey plexus. And again at this gestational age, that's about what you can see of the brain. There's not a lot of cortex that has developed yet. Um hydrocephalus. You may or may not see this early in gestation. This is a fetus actually that was seen at about 14 weeks. And um this is too much fluid in front of the core Oid plexus. You can see here the cord plexus is pushed posterior early. It kind of looks like saddlebags or it looks like actually that island in maine that arcadia National Park is on that. I can never remember the name of. Um But that is not a normal appearance in this Patient when she came back at 16 or 17 weeks of gestation, there was severe hydrocephalus in this fetus. So again, if you compare this image to this clearly this is abnormal. But just looking at this without thinking about whether that um Corey plexus is in the right place. You might miss a diagnosis of of hydrocephalus. So looking at the face, you want to look at the profile the nasal bone and the orbits. Here is a nice normal looking profile. Here's the chin, here's the nose. Here, cleft lip and palate can be difficult to visualize, but I'll show a picture of what that can look like. And again, findings of the face can be pretty subtle um And you really have to get just the right picture and have a high index of suspicion again and know some of the subtle findings that uh we should be looking for. So the thorax um is uh again one of the next organs. We want to look at our organ systems or fetal areas. And looking at the thorax. You want to see that there's a four chamber view of the heart. Um And where the cardiac axis is pointing and look to assure that there's not fluid that has collected in the chest. So you want to look at the location of the heart and again, lack of fusions. This is an image that is a fetus with diaphragmatic hernia. So here's the heart. It's pushed over to the left and here is the or to the right and here is the fetal stomach up in the chest which is not where it should be. You should not be able to see the stomach and the heart uh next to each other in the in the fetal chest. Our cardiologist will do a fetal echocardiogram in the late first trimester. And again if you start to do this, it is surprising how much detail of the fetal heart. Um One is able to see at this gestational age. Um If you uh if you pay attention the heart is tiny and it's complicated and there's arteries and veins but they have developed by this gestational age and one can um One can image them and diagnose many types of congenital heart disease. So by 13 to 14 weeks you should be able to see the four chamber view and the outflow tracts. And again there are many, many reports describing late first trimester uh echocardiogram. So in patients who are at particularly high risk for congenital heart disease, um we do uh look carefully at the heart. And sometimes our cardiologist will do a fetal echocardiogram. So this is a video showing a the four chamber view of the heart at 13 weeks gestation. And you can see in this clip, you could the stomach went flying by. So the stomach is below the heart in the right place and you can see a nice four chamber view there. But you can see if you look carefully here, there is a connection between the two ventricles and this is a fetus with a ventricular septal defect. Turning on color can help you delineate the chambers of the heart and make it um make it easier to see. So we use a lot of color Doppler uh in these examinations of the heart at this gestational age. So um this was data from a study where they looked at detection rates of uh fetal echocardiogram in the first trimester versus the second trimester to see what they were able to detect. And this was 870 cases. So it was a big series. And again, they compared first trimester diagnosis to second trimester diagnosis. And in this cohort there were 36 cases of abnormalities of fetal heart. So it was a pie risk um population and 32 Cases were discordant. So there were 36, there were abnormal first trimester and second trimester agreed there were almost as many cases that were discordant. So some of those were false positive diagnoses in the first trimester. So definitely if we see something and there's any uncertainty that needs to be confirmed. There were some major congenital heart defects that were missed in the first trimester and some things even that turned out to be serious are just subtle and hard to see. And then there were some where there were differences in the diagnosis. So something was suspected in the first trimester, but the actual diagnosis in the second trimester was was somewhat different. So first trimester echocardiogram and cardiac diagnosis is feasible, but I think it is important to appreciate that there are definitely limitations to what we can diagnose and the accuracy. One of the other areas that we see a lot of fetal abnormalities is in the ventral wall, and ventral wall defects are another category of structural anomaly that are readily detected in the late first trimester. So gastro ski sys and emm fallacy are both defects of the anterior abdominal wall of the fetus, where intestines and other abdominal structures are exterior arised with gastro synthesis. It's just a hole in the abdominal wall that the intestines are floating out through. So here is a fetal profile and here is intestines on the outside and you can see that irregularity that's just free floating intestinal contents. And here is an M phallus eel and fallacy eel is a defect of the umbilical cord where the intestines are actually exterior to the fetus, but within the umbilical cord. So it makes a sort of assist here or a membrane covered defect that is nice and round and globular and looks quite different than this when you see them side by side. Um This fetus also has a big new cool translucency here and um phallus seals are highly associated with chromosome abnormalities and big nuclear translucency is actually pretty common. But again, these should be readily detected at the time of this first trimester, an atomic survey and these are three D images that kind of show these and how they look a little bit different. Here's a gastro ski sis it's kind of irregular and they're typically on the right side of the fetus a little bit. And here's an m fallacy, real nice round globular um structure again, right at the base of the umbilical cord. So one thing important to know and to keep in mind, I talked earlier about developmental changes and how one has to be aware of normal development and physiology. So early in pregnancy it is normal to have a little bit of the intestines in the base of the umbilical cord. So this is a cross section through the abdomen of an early uh 11 week fetus. And this is the base of the umbilical cord with some bowel herniated into it. That is actually normal. It looks big in that image. But that's a normal finding at 11 weeks. And this is the same patient came back at 18 weeks. Here's the stomach, here's the spine. This is a cross section through the abdomen. This is the umbilical cord insertion and that um herniation of intestine is gone. Um It has gone back into the abdomen which is the normal process of development. So if you see um chord with Intestinal Contents in it at 11 weeks, sometimes that can be abnormal. Sometimes it's normal. Often you have to have these patients come back. All right. What else can we see stomach and kidneys can both be seen uh in the in the late first trimester, here's the stomach. You should always see that by 11 or 12 weeks of pregnancy. And here are the fetal kidneys. Here's one kidney and here's the other kidney. Here's the renal pelvis here and here again. With Adjusting your ultrasound settings. You should be able to see the kidneys by 12 weeks of gestation. Um Using um color can help us identify the bladder. So here's the field pelvis. Here are the legs and here's the bladder. This black circle here, this is a two vessel umbilical cord. So we turn on color, which can help us identify the bladder. Here's the bladder and again, this is a two vessel umbilical cord, which we see pretty often usually turns out to be um just a normal a normal variant. One thing we sometimes see early in pregnancy is an enlarged bladder. So here is a cross section through a fetus and here is a quite enlarged bladder. It's definitely not normal to have the bladder be that big. So this can be a sign of bladder outlet obstruction. Um and in about 20% of fetuses, when you see a big bladder like that, it turns out that the fetus has a chromosome problem. But the other 80% of the time the fetus has normal chromosomes. And if the bladder is mildly enlarged and you know what What's mild and what's severe, I think there's not great agreement on that. But if it is less than seven, usually that's pretty Falls in the category of mild enlargement. Um most of those will actually resolve. So this is a pretty prominent bladder but that is one that certainly could resolve and again, almost 90% of the time. If the patient comes back in a couple of weeks, the bladder will be back down to normal and why that is, it's probably just that the urethra which connects the bladder to the amniotic fluid. In some cases just Kanye lies is a little bit late in development and the bladder gets bigger and bigger until finally that process is complete in the bladder empties in these fetuses go on to be perfectly normal. So seeing it in large bladder can be relatively common and although these patients are at high risk to have a chromosome abnormality or a bladder outlet obstruction that is severe and leads to complications. In many cases it will resolve. And we see a fair number of patients for a second opinion for an enlarged bladder. This is one of the places where we can be kind of the the good guys or the hero patients come to us for their second opinion by the time they get to us, the enlarged bladder is gone and we can just be giving the patient good news. So again, really important to have short interval follow up for this particular finding. Okay, skeletal anomalies. So looking at the skeleton, we want to look at several structures. We want to look at the cranial vault, all of the long bones including the hands and feet. And we can see the fingers and toes actually pretty well at this age the spine starts to Aasif i at about 10 weeks of gestation. So in the late first trimester we can see the bony spine, skyfall scoliosis where the spine is irregular. We can identify and skeletal dysplasia is um we can detect although it can be sometimes tricky to make a precise diagnosis. Um as some of the features that tell us the diagnosis later on in pregnancy can be hard to see in detail at this gestational age. So again the long bones are easily visualized patients love this cute picture of the hand and the fingers. Um Here are the legs and you can see these are the feet. Here the ankles are kind of crossed over. They like that position. And here is a foot and here are the toes. You can't make out the individual toes necessarily all that well. But you can see that there are toes there. Um and this was actually a patient. She was 36. She came in for her new cool translucency screening. Here's a nice little profile shot, here's her new cool translucency which is a little prominent but probably normal and here is the fetal heart and this patient actually the upper extremities were quite abnormal. So here you can see this angular waited upper extremity. Here's a nice three D. Picture where you can see it really clearly and here again you can see it. Uh you can see it over here and this was something, there's a condition called holt Oram syndrome that includes heart defect and upper extremity abnormalities. And actually um this is a picture of a child with Holt Oram syndrome. It's not the same case that I showed you. But you can see those arms are exactly what we saw by ultrasound in this particular patient. We were able to do a micro array and make a diagnosis for this patient. This is something that often runs in families, It's autism, a dominant meaning if someone has it, there's a 50 50 chance their Children will have it in this particular family. It actually um was not something that was president present in the family. But for this patient, quite early in her pregnancy, we were able to make a very precise diagnosis and tell her, you know, the the upper extremities had this this finding and there was a ventricular septal defect which is a pretty subtle heart defect. But these Children, we don't expect them to have learning difficulties or other medical problems. So we were able to give her very specific information about her pregnancy so that she could um make decisions about further testing and how she what she wanted to do. As far as continuing the pregnancy. Um here is a fetal spine. And over here on the left. This is a normal spine. You can see the individual vertebrae nicely ossified here on the left and here on the right. This this dark area is the spinal cord itself. But you don't really see that bony spine. So sometimes at 10 or 11 weeks, the spine may just be not well ossified, but this was really pretty markedly unusual looking that we could not see the ossification centers or the vertebrae of the uh of the spine. And again, you can see here, you can't really see the spine quite as well as you would expect. Looking at the cranium, you know, this is the outside of the head. And again, you should see that bright white reflective bone. So that was subtle, but it did not look normal. And then here is an arm here and you can see this is very irregular, it's not straight, it's sort of um fractured and compressed and is definitely not normal appearance of the right arm. So we were very suspicious that this was some kind of a skeletal dysplasia. Although these findings are non specific enough, we couldn't tell the patient exactly what the diagnosis um was. So we um said, you know, there are under ossified bones, bent and fractured extremities. And we were able to do X. Um sequencing in this pregnancy and make a diagnosis of something called hipAA phosphate asIA, which is a type of skeletal dysplasia that can cause these findings. But it's relatively Rare. Making that diagnosis for this family was really important because this actually is a genetic disorder that's inherited. Um so both of the parents were carriers and there was a 25% chance in each of her future pregnancies of having a recurrence. So this patient with this information Is planning to have in vitro fertilization in preimplantation, genetic testing to prevent recurrence in a future pregnancy. So all of this we were able to find out for her before she was even 20 weeks when normally is when people would be getting their their an atomic survey. So I think you know between the power of this more advanced ultrasound and adding some of the genomic sequencing were able to do. Now we really are able to make these very precise diagnoses um in in pregnancy. Okay, so spinal imaging, I had mentioned earlier that spinal abnormalities um and spina bifida in particular are some of the things that can be challenging to diagnose in the first trimester. And these are data from a study where this group looked at spinal abnormalities and in their new cool translucency program. How many did they diagnose? And how many were missed? So there were six cases of isolated spina bifida. So fetuses with spina bifida and no other abnormalities. And two of those were detected. But four of those were missed and those that were detected had significant Kifah scoliosis. So usually spina bifida, the spine is straight, it just has an opening in it. But sometimes there can be a key emphasis or scoliosis and the spine can be quite bent. And in this particular series those were the cases that were detected. Not surprisingly, it's easier to see that. But routine ultrasound at the time of a nuclear translucency really does not usually pick up spina bifida and it is important limitation for um patients to understand because it is relatively common. Um There is there are some findings in the brain that are subtle but that can be indications of spina bifida. So there's something called the intracranial translucency that is abnormal in fetuses with open spina bifida. So here is a normal fetal profile and this arrow points to see these two white lines here in between those is dark fluid and that is the fourth ventricle. And so this is the brain stem and this parrot line or this dark space is parallel to this dark space and that is normal. This is a fetus on the right where it says abnormal dead giveaway. This is a fetus with spina bifida. So here is the brain stem and here is the dark fluid but parallel there's no dark space here parallel to this one. So it's compressed because there is an open spina bifida making the cranial findings abnormal, this is subtle, it's not easy to see, We look at this and when you can see it and it's normal. That's great. When you see something like what's on the right it's just often you can't tell if it's really abnormal or if it's just difficulty um with imaging because of the fetal position. So again this is subtle. Um and hard to really make a diagnosis. But if we do see findings that were concerned about in the head will sometimes that will prompt us to do and uh and a vaginal ultrasound to look much more carefully at the lower spine. And here in this particular case there is a spinal defect that was hard to see trans abdominal early but um more evident by trans vaginal ultrasound. So again the subtle brain findings can prompt careful evaluation of the spine and having the patient potentially come back a little bit sooner for follow up ultrasound. So the intracranial translucency. Again there's been lots of reports on this um for diagnosing Spina Bifida. This was a retrospective study where they looked at 200 cases. Um Eight of them there was open spina bifida and they were able to detect about half and there were a couple of false positives. So the bottom line was when the intracranial translucency is nicely scene spite of if it is pretty reliably excluded it's very reassuring. But if you can't see it it's much more likely to be just technical and not a real spina bifida. So when we are concerned we will do any vaginal ultrasound look more carefully. And if we really can't resolve it, have the patient come back in a couple of weeks instead of waiting for that 20 week examination. Um This is another finding that one can look at to assess for spina bifida. Again, it's the same kind of thing. The fourth ventricle in the brain is displaced posterior early. And this is just a different way of looking at that. So this is a cross section through the head. This is the fourth ventricle here and there should be some distance between that and the back of the head in this abnormal fetus. Here's that fourth ventricle and you can see it is much closer to the cranium posterior early, which is abnormal. This is very clear when you're looking at these two images side by side. Um but when you're just, you know, doing an ultrasound and just looking at this again, it can be helpful to look at that, but it can be pretty subtle. Um So we again, we look at these things but we definitely explain to patients that spina bifida is a one of the one of the limitations is that this is not the best way to make that diagnosis. So thinking about these first trimester, an atomic scans and what we are and are not able to diagnose. Um there's been a number of patients of papers published on this. Um this one is from 2011. And although ultrasound has gotten better, more series have been published, these numbers really hold up pretty well. So in this series they looked at over 45,000 cases And they evaluated all of the fetuses with non chromosomal abnormalities, of which there were 488 or about 1.1%, which is about what you expect. And they were able to detect just under half of them at the 11 to 14 week um exam and going through the things that were diagnosed in the things that were not diagnosed, it was basically what we would expect. So 100% of cases of a cranium and a low bar holo pros and Stephanie. Remember I said we should always diagnose those ventral wall defects like gastro ski sys and emm fallacy eel meg assistance, which is an enlarged bladder in something called body stock anomaly, which is a very severe disruption of the fetus. But things like cleft lip and palate very hard to diagnose spina bifida. They only diagnosed 14% and congenital heart defects. So again, some of these are subtle findings. Some of these there are developmental reasons that we can't diagnose them until later in the pregnancy. And again, things like A genesis of the corpus callosum vermillion, a genesis lung masses, bowel obstruction. Those things just don't develop till later in pregnancy. We're not going to see them at 11-14 weeks. So this is another, this is an interesting patient that we actually saw quite recently. Um She was a 37 year old. This was her first pregnancy and she had cell free DNA screening N. I. P. T. That was positive for trisomy 13. So she's about 12 weeks pregnant and she came in for assessment and I saw her and said you know this is a cross section through the abdomen. And you know we looked at this is the umbilical cord. Is there a little bit of bowel in the base of the umbilical cord? Or is that just an artifact of imaging given her history? I was quite concerned that that was actually a small handful a seal. And um it's hard to tell in this picture but here is color in what should be a four chamber view of the heart and the heart definitely looked to be abnormal. So we were quite concerned that this actually was fetus did have trisomy 13. In fact the patient had a CVS. And we confirmed the diagnosis of trisomy 13. So we think of that diagnosis as something that has severe anomalies that should be easily detected. But again some of these findings can be can be quite uh subtle. And this was a was a real and fallacy. Well okay so what are the indications for doing these first trimester? An atomic scans? Hopefully I have convinced you that they can be very helpful. Um But they are time consuming and not every patient um needs to have a detailed uh an atomic survey in the first trimester, It doesn't diagnose everything. So it's not a replacement for a second trimester scan. You know, I want to emphasize that if patients are only gonna have one ultrasound in their pregnancy, the best time to do that is still 18-20 weeks. But in patients who are at increased risk for structural abnormalities, this is a very helpful alternative or option. Um So the ai um criteria for indications for a first trimester um exam. Our patients at increased risk for fetal or placental abnormality that may be detectable by ultrasound in the late first trimester. So that could include people with a previous fetus or child with an abnormality. And this is probably the most common indication that we see people who have had a bad experience in the past really benefit from that early most of the time. Reassurance patients who have abnormal screening, I showed the case of cell free DNA that was positive for try somebody. 13. Um The other thing that we see a lot is people who have a new cool translucency screening and the at that time there is a suspicion that there might be other abnormalities. And those patients come to us for spending the time to do a more detailed analysis or examination of all the anatomy patients with poorly controlled pre gestational diabetes are at high risk for anomalies. Um And this exam can be very helpful and then patients who have a very high B. M. I. So patients with a high B. M. I can be very difficult to image. And although we think later in pregnancy it's going to be easier to see actually at 12 or 13 weeks, if you do a vaginal ultrasound, you don't have to image through the panis, you can get closer to the fetus and it may be the best time to um see the anatomy as compared to later in pregnancy. So patients with a high B. M. I. Um this can be a good alternative. So in conclusion about half of anomalies are detectable in the first trimester. Um Some things we should always detect and we we usually do and there are some things that just the limitations of of development we will we will never diagnose. But most things are of variable detection and I think that um this is really where the field is going. I think more and more patients are going to be to benefit from having this early kind of examination. And it's just important to recognize how things change developmentally in those things that we we can and can't see and detect. Um So great benefits to patients of early detection and again from most patients, early reassurance, very important to think to be aware of over calling abnormalities things like in large bladder and physiologic bowel herniation. Some of those examples that I uh that I showed. Thank you very much for your time. And if you would like to refer patients, we see patients for first trimester. An atomic surveys through the UCSF fetal treatment center. And you can contact us through the link below or by calling the fetal treatment center phone number. And again we see patients every week. So do feel free to contact us if you have patients that you think would benefit from this kind of examination.