Prenatal intervention for Fetal Urinary Tract Obstruction

Newborn urinary tract obstructions can be a devastating problem, but fortunately now there's actually prenatal interventions for fetal urinary tract obstruction. Here's Doctor Jose Pierro from Cincinnati Children's Hospital Funeral Center explaining. The first thing is that to offer any fetal therapy, we need to make a good diagnosis. So to help diagnose some of these fetal problems in utero, we actually need ultrasound to help us figure out what's going on. But what exactly are we looking for in ultrasound in these cases? Basically, in the prenatal ultrasonography, looking at this keyhole sign, the bladder thickness, how much amniotic fluid we have around the baby, and finally, the fetal sex. Wait, what? Jose, why do you need to know the gender of the fetus? If it's a male and potential posterior urethral valves. Ah, I see now. So in males, you can diagnose posterior urethral valves, which we know is amenable to fetal intervention. All right, so I get why urinary tract obstruction is a problem, and I get why we need to fix it, but why fix it in utero? Is there some problem that the urinary tract obstruction causes in the fetus? We have pulmonary hypoplasia because insufficient lungs as a result of the anidramius, renal insufficiency in many cases because this obstructive neuropathy creating renal dysplasia. We have the bladder dysfunction of this distended bladder without no cycling bing. So in order to achieve our therapeutic goals, we need To target the lungs, the kidney, and the bladder because we know the lungs produce lethal consequences. Kidneys produce renal insufficiency, morbidity, mortality, and also needs of transplant. And finally, the bladder can produce bladder dysfunction with infections and a lot of problems for these babies. OK, so we understand now that we need to protect the lungs, the kidney, and the bladder to prevent serious postnatal complications. But how exactly do we do that? Let's start with the lungs. To treat the lungs, we will need to restore the amniotic fluid around the baby to enhance normal lung development. OK, got it. What about the kidneys and the bladder? To improve the kidneys, we can to try the compression. To improve the bladder, we need to some kind of let the muscle, the detrosor for cycling contractions and better function. OK, so those are the goals of fetal therapy, but in order to have successful outcomes, we need to identify a good candidate. And for that, we need to look at renal function. Now, how exactly do we measure their renal function? We need to base our evaluation on the bladder tap using the fetal urine analysis, using the ultrasound to recognize the quality of the renal parenchyma and there is cystic dysplasia or not, and most importantly, In my opinion, the bladder refilling after the bladder tap. OK, so let's talk about bladder tap or vesicocentesis. This is the idea of sticking a needle into the bladder to aspirate out urine to send it for urinalysis. How exactly do we do that in utero? We put a needle by ultrasound guidance and we target the bladder that is distended in this fetus so we can remove a significant amount of urine that usually is all urine for analysis. One side benefit of the bladder tap is if you actually aspirate out the urine and you see the bladder refill with urine again, you now know that the fetus has the ability to make urine. So in summary, electrolytes, refilling and ultrasounds, that will be our assessment of the renal function. So that's a wide spectrum of fetal urinary obstructions. We actually can see severe renal dysplasia where the baby makes no urine at all. We have no option to improve these kidneys at all. The only goal of the treatment will be a pulmonary survivor, to save the land by replacing the amniotic fluid also. We can see moderate or borderline renal dysplasia where the kidneys make a small amount of urine. This will be a more difficult situation because probably we'll be late on save any kidney function, but still we can save the lung and provide these babies the option of renal transplant if it's necessary. And then there's those cases where there's no renal dysplasia and the kidneys make plenty of urine. And those are theoretically keep safe the kidney and try to rescue the lung as well. So it's when uh derivative techniques will have a role. OK, so now let's talk about the actual fetal intervention. We basically have three categories percutaneous, fetoscopic, and open surgery. Percutaneously, we can take the urine with. bladder aspiration, we can place a shunt. We can make infusions all percutaneously. Cystoscopy will be a good option for fetal cystoscopy and ureteral catheterization or valve ablation. The open fetal surgery was tried to produce really open vesicostomy or cutaneous uteostomies. OK, so let's talk about the vesico amniotic shunt. This is actually one of the more widely used techniques, and there's a whole array of different ways of doing it. Basically, the more common in the market is the Rodeck, the Harrisons, or Cook, and finally, recently the Summaex that it's more used in Europe. But how exactly do we do it? What's the procedure like? This is a recreation of how we do percutaneously by ultrasound guidance. We can place a cannula with a trucker, sharp trucker inside so we can access the bladder and then push this pigtail, the half memory shape, so half of the catheter will be inside the bladder and the other half, once we remove. The outside cannula deploys inside the amniotic cavity for drainage of the urine. So if we go back and look through the data, there's actually a 98% success rate with the procedure, but there's a 15% complication rate. And the problem is, if there's a complication, it's pretty much 100% mortality because of loss of the amniotic fluid. Overall survival is about 50%, and of the survivors, 40% will eventually have end-stage renal disease. Let's dive a little deeper into the complications by looking at a study by Elder et al. in 1987. Basically, blockage, so inadequate shunt drainage, shun migration. Actually, shunt migration is pretty common as the fetuses often pull or dislodge the shunt. Preterm delivery um because from, we can have urinary ascitis when the drainage is not to the amniotic cavities, to the, to the abdomen. Actually, we can have choramionitis and also diatrogenic gastroschisis in the in the orifice of the of the abdomen and also more commonly probably abdominal or mental herniation. Let's see how efficient this procedure is. There was actually a trial done at Birmingham University where they looked at percutaneous shunting. In the trial, they compared shunting to expectant management. And although it was difficult to recruit patients for the study, only 15 versus 16 cases, there was a trend. There was preliminary results showing an improvement in perinatal survival in these fetuses with shunt. Another meta-analysis which looked at 9 papers showed a perinatal survival advantage in those who got the vesico amniotic shunt. However, 1 to 2 year survival or renal function was unclear. So, now let's talk about open fetal intervention. Where does that stand? The open approach makes a lot of limitations in terms of pre-term delivery for sure. So there was an an attempt, uh, uh, by Doctor Crober home here in Cincinnati and Doctor Lim to create fetal physicostomy by open approach. This is a video where you can see the umbilical cord insertion. So just below. With a minimal exposure in the uterus, you can attempt to create a hole in the abdominal wall and then marsupalize the bladder for complete drainage and then allow these babies to close spontaneously the vesicostomy postnatally. Like anything else, open fetal surgery has its own risks and benefits. Here are the things we need to consider with open fetal surgery. Of course, the problem is that you need a deep general anesthesia. It's very invasive. You need a maternal laparotomy and hysterotomy, and of course, there is more increased maternal and fetal risk with more prematurity. So now let's look at our data at Cincinnati Children's Hospital. We've had 6 male fetuses between 19 and 22 weeks of gestational age who all had anhydramnios and normal fetal urine electrolytes. They all had vasicostomies and postnatally they had complete decompression of the urinary tract system. But here's where it gets complicated. Although there were no maternal complications, only 2 of the 6 survived. OK, so now we've talked about percutaneous therapies, open therapies, and now that brings us to cytoscopy. Cytoscopy is an endoscopic procedure during pregnancy that gives us surgical access to the fetus, the amniotic cavity, the umbilical cord, and the fetal side of the placenta. A small incision is made on the mother's abdomen and the endoscope is inserted through the incision through the abdominal wall into the uterus, into the amniotic cavity. So what are the things we need to consider with cystoscopy? Basically, the problem we have with fetal cystoscopy to attempt these posteriurethral valves is the angulation we have. We can access very well the bladder, but sometimes it's very difficult to see well, the orientation in the posteriral valves during the surgery. OK, so when talking about fetal cystoscopy, there are two methods either percutaneous or mini laparotomy or a small incision. At Cincinnati Children's, they prefer the mini laparotomy approach because they get a great view of the posterior urethral valves. In this procedure, they put what are called T fasteners down which bring all the layers of the tissue together so they get a great view of the valves. So you can see here how we place the T fastener here when we can pull and put the scope just in between, orientated much better to the posterral valves. So while fetal cystoscopy is mostly used for diagnostic purposes, it actually can be used for therapeutic purposes as well, like in valve ablation. The goal is to fulgurate these valves and maintain open this urethra. In one study by Ruanoal, they actually looked at the therapeutic benefit of fetal cystoscopy, and what they found was that there was a 60% survival in those patients compared to the control group, which was 10%. Sometimes a transurethral catheter can be placed in combination with laser therapy. In one particular case, in a 23 week fetus. They actually placed a wire to identify and get access to the valves and then use the laser. And finally, we passed again the, the wire and we deployed the transurethral catheter as a second treatment in combination with the laser. OK, so it appears that fetal cystoscopy may have the best outcomes. If you look at this study in 2015 by Ruano et al, they actually compared the survival between. Fetal cystoscopy, VA shunting, and nothing, and they found that cystoscopy had a 66% survival. VA shunting had a 60% survival, and doing nothing, or the control group had a 17% survival. They also found a distinct, unique advantage that fetal cystoscopy seemed to decrease the incidence of chronic kidney disease in patients with posterior urethral valves. But in 2019 VA study, they actually found no difference between VA shunting and fetal cystoscopy as it pertains to chronic kidney disease or survival. So in summary, cystoscopic ablation of uh erral valves with a catheterization may improve pulmonary outcome and maybe renal sequela and bladder function. We need to do early detection and select very well the, the patients, of course, and of course, urethral trician cloaca uh will require different management. Also, in some cases, you can have a urethrocele, which can actually cause a bladder obstruction as it prolapses through the posterior urethra. And in females, because of the short distance of the urethra, it can actually prolapse all the way out. And this can be treated surgically by either doing colon or puncturing or cystoscopy assisted laser incision to decompress the cyst and relieve the obstruction. So let's talk about what happens when you have kidney dysplasia and minimal urine output. Only option is trying to rescue the lungs by placing fluid from outside. They are not candidates for shunt, for cystoscopy. We can restore the amniotic fluid and try a pulmonary survivor. So what are the methods we have? So we have the possibility. With needle to do repeated and serial amnio infusions and that will need once a week initially and probably twice a week in the late station. The other option that we offer in Cincinnati is the possibility of placing an amnio port. Amnia port is a meta port used for intravascular medication and parenteral nutrition. It can actually be implanted inside the uterus so we can access very easily underneath the skin every time we want for replacement of fluid, and this is what happens before and after the amnio infusion so we can repopulate the fluid very easily. Since the amnia port is a relatively new technique, there's actually only one paper that's looked at its outcomes, and the results are pretty good. There was no cases of fetal death related to the procedure, and in all cases there was complete restoration of amniotic fluid following the procedure. Only 6 of the 8 fetuses actually had pulmonary hypoplasia at birth. Finally, we need to recognize that, not all cases will need fetal intervention. For that reason, this selection is important to have a very good diagnosis, very good multidisciplinary team to approach these uh cases in specialized centers.