Bethany and Molly discuss the history of HDFN and Alloimmunization. From the 1600s with a strange record of infant mortality to early attempts to hit an umbilical cord with a needle using only an x-ray and paper clips. They tell the story of the true state of disease management today using direct quotes from affected families. They also look to the future with hopes of new preventative medicines that could change the treatment of HDFN.
Bethany and Molly discuss the history of HDFN and Alloimmunization. From the 1600s with a strange record of infant mortality to early attempts to hit an umbilical cord with a needle using only an x-ray and paper clips. They tell the story of the true state of disease management today using direct quotes from affected families. They also look to the future with hopes of new preventative medicines that could change the treatment of HDFN.
Episode themes:
Allo Hope Terminology Library https://allohopefoundation.org/library/terminology/
Guests: Dr. Ken Moise https://partnersincare.health/directory/kenneth-moise
Links mentioned in this episode:
The History of HDFN (timeline on AHF website): https://allohopefoundation.org/library/history/
Mari’s article on MCA Dopplers: https://www.nejm.org/doi/full/10.1056/nejm200001063420102
Dr. Moise’s editorial from New England Journal of Medicine: https://www.nejm.org/doi/full/10.1056/NEJMe068071
Nipocalimab trial: https://clinicaltrials.gov/ct2/show/NCT04951622
Research for this episode provided by Bethany Weathersby and Molly Sherwood of the Allo Hope Foundation. Find more information at https://allohopefoundation.org
The Allo Podcast is produced and edited by https://www.mediaclub.co
Bethany Weathersby:
The information shared on The Allo Podcast is not intended as medical advice.
Molly Sherwood:
Your medical care decisions should be made in consultation with your physician who is familiar with your specific case.
Bethany Weathersby:
Hey, welcome to The Allo Podcast from the Allo Hope Foundation. I'm Bethany Weathersby.
Molly Sherwood:
And I'm Molly Sherwood.
Bethany Weathersby:
In this episode, we are discussing the past, present, and future of HDFN treatments, prevention, monitoring, all of it. And we are so excited to talk about this topic. I think it's fascinating to hear how women of the past were treated or not treated during their alloimmunized pregnancies, and it's incredible to see how far we've come in such a short amount of time in the past few decades.
Molly Sherwood:
I know. We have a total grab bag today. It's like a variety pack of information. We have stuff about the past, how it used to be presented and treated or not, like you said, and then really cool innovations, which Dr. Moise was there for some of them. And so he talks about his own account, which is so cool. And then we talk about what's going on now, the reality of the disease now, and then our hopes for the future, and then cool little stories woven in between. It's going to be a fun one.
Bethany Weathersby:
And it hasn't even been that long since this disease was, I guess, acknowledged or discovered, right?
Molly Sherwood:
Yes, and even less time since it was actually treated. I mean, it's really in the last hundred years that people even tried to treat. And by treat, I mean delivered babies and then they did not die.
Bethany Weathersby:
Right.
Molly Sherwood:
Yeah. I'm excited to hear about Dr. Moise's account of this, and then we'll get to talk about the future, which I think looks even more promising than now for families facing this disease. So it'll be really nice to end on an encouraging note, but let's start with the not encouraging stuff. Let's talk about the past. By the way, all this stuff in the past is in our History of HDFN page that we have on our website. So we'll definitely link to that in the show notes. You want to kick us off, Bethany, talking about the beginning?
Bethany Weathersby:
Sure. All Right. Going back to the dark ages now.
Molly Sherwood:
Okay. Yes.
Bethany Weathersby:
Okay. So let's go all the way back to 1609 before the development of modern medicine when infant mortality was extremely high, often due to unknown causes. A French midwife delivered twins and kept a record of the birth, which we so appreciate now up here where we are in time.
Molly Sherwood:
Yes, thank you.
Bethany Weathersby:
And she noticed that there was something very wrong with the twins after they were born. One of the babies was very swollen. And some accounts say the baby was stillborn, other accounts say the baby died soon after birth. Either way, the baby was visibly sick and unfortunately did not survive. So the other twin seemed much better than the first twin, but over time, that baby developed severe jaundice and died several days later. And we now understand the swelling as hydrops and the severe jaundice as kernicterus, both of which are components of hemolytic disease of the fetus and newborn, HDFN. And this account from this French midwife of the twin's birth was the very first recorded description of HDFN. And then that was... So this is back 1609. So for the next 300 years, there were similar cases described in which newborns failed to survive. They were seeing these babies born with similar characteristics, but they just did not know what was causing this disease or how to treat it. I mean, so centuries went by before anything improved.
Molly Sherwood:
That's crazy.
Bethany Weathersby:
Yes.
Molly Sherwood:
Yeah. And it wasn't until the 20th century even that the underlying cause of HDFN was clarified because we now know it to be the mother's antibodies attacking the baby's red blood cells because of incompatible blood types. And so really, we're skipping hundreds of years forward to even get to where people started talking about this disease. So you were just talking about the 1600s, but then my next item is not until 1940. So fast forward all the way to 1940, there was an experiment involving rhesus monkeys. Rhesus is the type of monkeys. It's the species of monkey. And they took the blood from these monkeys and injected it into rabbits and Guinea pigs. And then they took that blood... So the rabbits and Guinea pigs developed antibodies to the monkey blood.
Bethany Weathersby:
Wow.
Molly Sherwood:
They took the rabbit and Guinea pig blood and put it on plates with human blood and found that in a lot of cases, it clumped together. That's what we call agglutination. And now, by the way, after babies are born, we do the DAT, direct agglutination test. That's the same thing, to see if the blood is clumping, to see if there's hemolytic disease going on.
Bethany Weathersby:
Wow. Can I just pause right there and just say this sounds like a horror movie, doesn't it? With the monkeys and the rabbits and the Guinea pigs and the human blood is mixing.
Molly Sherwood:
I know, right?
Bethany Weathersby:
And I'm just like, "This is horrific, but also amazing." Yes.
Molly Sherwood:
I know. It totally is. That's why I was very explicit to say that they did it in dishes, not just in live humans.
Bethany Weathersby:
Yeah. Oh, my gosh.
Molly Sherwood:
They just took the human blood out and then put it together on plates.
Bethany Weathersby:
Great. Okay.
Molly Sherwood:
So that was good, I guess.
Bethany Weathersby:
Yeah. Sorry. Sorry to interrupt. Go ahead.
Molly Sherwood:
Anyway, so that discovery is what led to it being called the Rhesus factor, Rh, and Rhesus disease. It actually just came from the species of monkeys that were used in that study in 1940.
Bethany Weathersby:
That is so interesting.
Molly Sherwood:
It is super interesting. Also, in the 1940s, once the disease became identified in the women, it could only be treated through early delivery. And that still resulted in super high neonatal mortality because you couldn't actually monitor the baby to see how sick the baby was in utero, and then they would just deliver them early and they could die still of the disease or of prematurity.
Bethany Weathersby:
That's sad.
Molly Sherwood:
And that was still something. It was an actual treatment, I suppose.
Bethany Weathersby:
Right. Right.
Molly Sherwood:
But things started to take a little bit of a more positive turn in the '50s and '60s. So in 1958, researchers performed the first analysis of amniotic fluid, which is the water that's floating around the baby in the womb, and found bilirubin, which led to the new standard monitoring protocol being weekly amniocentesis to monitor baby's anemia because amniocentesis is just to withdraw some amniotic fluid and test it. So that became a way to check for anemia, but keep in mind, there's no ultrasound at the time either. So you just stick a needle in there often every week to check the baby.
Bethany Weathersby:
I would hate that as a patient.
Molly Sherwood:
I know. I know. And it wasn't until around this time also that phototherapy units were developed for babies who had high bilirubin. And so without this, babies could progress to have severe brain damage and death. So that was also a wonderful development for after birth treatment for babies with this disease.
Bethany Weathersby:
Yes. And think about how many babies need phototherapy after they're born for high bilirubin.
Molly Sherwood:
Oh, my gosh.
Bethany Weathersby:
I can't imagine that all of the babies and families before the 1960s or 1950s had no treatment for high bilirubin, I guess, besides the sun.
Molly Sherwood:
I know. Yes, I do. I have heard stories of people just laying their naked babies out in the sun for as long as possible.
Bethany Weathersby:
Yeah. Oh, my goodness. Right.
Molly Sherwood:
And then, we're going to talk about this more, you'll have to tee us up for this, but in 1963, Lily conducted the first intraperitoneal intrauterine transfusion. So putting the needle into the baby's tummy and giving a blood transfusion that way through the mother's tummy.
Bethany Weathersby:
Wow.
Molly Sherwood:
So mom's tummy into baby's tummy. They injected the donor blood directly into the fetus' abdomen.
Bethany Weathersby:
So Dr. Moise actually has a really fascinating firsthand account of the development of IPTs, which is the intraperitoneal transfusions that you were just talking about, Molly, and the eventual evolution into what we now call intrauterine transfusions, which include the transfusion into the umbilical cord as well. And remember when we mentioned that the babies were monitored weekly with that amniocentesis, the needle going in and removing the fluid to check for bilirubin?
Molly Sherwood:
Mm-hmm.
Bethany Weathersby:
Well, Dr. Moise walks us through the development of the MCA Doppler scans, and that is what we now use for non-invasive monitoring for fetal anemia instead of that amniocentesis.
Molly Sherwood:
Yes.
Bethany Weathersby:
Okay. So let's hear this super fascinating account from Dr. Moise.
Dr. Ken Moise:
I had the privilege of being invited to be a visiting professor in Auckland, New Zealand, and that's where William Lily decided to do his first transfusion on Rh patients. Why in this little bitty island of New Zealand, this man was in the right place at the right time. And unfortunately, William Lily did not live very long, but I met his radiologist that helped him do the procedures. And he was 92 and sharp as a tack. And we had breakfast together and he told me the stories of those first procedures. And later, I got copies of the x-rays. There was no ultrasound. This is 1963. No ultrasound.
Bethany Weathersby:
Wow.
Dr. Ken Moise:
And Lily decided to try this, which was really incredible. And to know where to put the needle in the baby, he decided to tape paperclips on the mom's abdomen and take an x-ray. And then based on the little numbers by the clips, he'd say, "Well, I think I need to put the needle right about there." And he would blindly put a needle into a baby's belly and push blood in. And it took three different babies before he had a success, but ultimately, he succeeded in transfusing that fetus in utero. And that was the advent, truly, of any fetal therapy. There was no fetal therapy until then. But to think that this man did this with just a static x-ray and was successful, which led to what we do today, is just amazing. Until that time, if you were diagnosed with severe disease, your baby died. There was nothing could be done.
And it was back in the '80s when I started that we first started thinking about putting blood in the umbilical cord directly. So up until '63 to '85, everybody did what's called intraperitoneal transfusions with blood put in the belly. And when I first came to Baylor in Houston, we were still doing those. In fact, we still do them today, but we're doing them very different. We would put a needle into the belly and then we would put a plastic catheter through the needle into the baby's belly and then pull the needle out. And then my job was to come back to the bedside later and hook the blood up to it, and push the blood through the plastic catheter and then pull it out, and pull it out of mom's belly. And that's how we did transfusion successfully for a long time.
I remember the first time I went to a meeting and we heard a Frenchman talk about hitting the umbilical cord, and we thought he was crazy. How could you purposely hit the cord and not lose the baby? And he was doing it for a different disease, an infection in the mother called toxoplasmosis, but he showed us the loss rate was 1%. So we all came back with no training and said, "Well, we need to do this." And I was with my mentor at the time when he tried to do the first intervascular transfusion. I was the fellow at the time, and I think I counted eight times that he tried to stick the cord, and I was just cringing as he kept sticking this cord. He never got in because we didn't know all the different finesseful techniques. But I was there the first time he finally got in and we put blood into the baby, and that was the most exhilarating thing to watch blood go into this baby through the umbilical cord.
So that's a big change. That was a major breakthrough to put blood directly into the baby. And then I became an attending and this young Italian man who barely spoke English came to work with us. I remember he worked in the Department of Cardiology and they ran out of money. And so he came to me and said, "Could you pay me a little bit of money to stay here?" He barely could speak English. His name was Giancarlo Mari. And he said, "I want to work with you on this Rh situation and I want to come up with a way to tell when the baby's anemic." And what he would do before every intrauterine transfusion is check out every blood vessel in the baby. I mean, he'd spend an hour with these poor women looking at everything in their baby's body. And ultimately, he chose the middle cerebral artery as the vessel to look at to decide if the baby was anemic because we would do the blood transfusion right after that. And eventually, he could compare his numbers to our numbers.
And I asked him, "Why did you pick the middle cerebral artery?" And he said, "Well, it's easy," in his broken Italian, "there's two of them. You get one or you can get the other one, but you could always find one." And it was a few years later that he finally published his paper to show that we could look at a specialized type of ultrasound in the brain and tell if a baby's anemic. And I think of all the things I've helped do... And I didn't do the study. I mean, I helped him with the study, but he actually collected the data. That's been the biggest change in what we've done because he has saved countless babies from not having procedures. But more importantly, and I think there's some data just came out of the group in the Netherlands, we are seeing babies that aren't as sick. So it used to be a baby had to be hydropic to get referred to a center and that baby was very ill. And now, we're seeing pregnancies much earlier because the MCA Doppler is suggesting the baby's anemic, even when it's not hydropic, especially early in pregnancy.
So that one technique, and I was lucky enough, after another study was done, to confirm John Carlos' findings, I got to write the editorial in the New England Journal of Medicine that accompanied it. And I stayed up all night trying to think of a catchy name because you always want a catchy name when you're invited to write an editorial, and I came up with "It's Time to Put the Needles Away." We were doing amniocentesis every week in these women to look for yellow jaundice as the only way to tell when their babies were getting sick. And when the MCA Doppler was confirmed as an accurate technique, we stopped doing amnios in these patients, and it was just such a wonderful thing for them not to have a needle put in their belly every week to see if their baby was getting sick. And to your point Bethany, we found out that those babies with Kell, amniocentesis didn't work. So MCAs became even more diagnostic in the Kell babies because the amniocentesis technique worked for Rh, but didn't work for Kell.
Bethany Weathersby:
Wow.
Dr. Ken Moise:
So the MCA has probably saved more Kell babies by picking up the anemia.
Bethany Weathersby:
That's amazing.
Dr. Ken Moise:
And there've been other things that have come up like free DNA for diagnosis without having to do an amniocentesis and things of the sort, but I think of all the things, the intravascular transfusion in the '80s and then the MCA Doppler in the early '90s were the big breakthroughs.
Bethany Weathersby:
Wow, that is so amazing to hear.
Molly Sherwood:
That's so cool.
Bethany Weathersby:
I almost feel speechless. It's one thing to read about historical events, but it's a totally different experience to actually hear an account of the events from a person who was there.
Molly Sherwood:
Yes, I know. We need to get... Let's get that article from Mari and then also Moise's editorial. I'll get that in the show notes and put that in there.
Bethany Weathersby:
Yes. And we are so lucky that Dr. Moise serves actively as a member of our medical advisory board, and he develops very helpful guidance that we share for patients and providers today. So he is a jewel, a gift to all of us. And also, just thinking about, I mean, these doctors, these are the pioneers in this field who tried these new things and took risks. And now, Molly, you and I have... I don't know what the past tense is of reap. Reaped? Rept? But we rept...
Molly Sherwood:
Reaped.
Bethany Weathersby:
I don't know why that sounds weird. We've re-reapeaned. We have reaped the benefits of their work and we appreciate them so much. But also, okay, on the flip side, the women, honestly, you guys are the heroes.
Molly Sherwood:
Yes, I was literally... I had the exact same thought. I was thinking about when to have that same interjection. I completely agree with you.
Bethany Weathersby:
Tell me your thoughts on that.
Molly Sherwood:
No, on both ends, can you imagine the courage it takes for a physician to do something so outrageous and risky, when they risk their own reputation and their own outcomes, and they risk hurting a patient? That is just amazing that they're willing to do that for the sake of development of science. And then two, that these women are willing to be an experiment. And the sacrifices some of them made, of course, it sounds like it wasn't even successful the first couple times, for example, with the intraperitoneal transfusions. It's just an immense sacrifice, such a valuable contribution from the patients and the doctors. It's amazing.
Bethany Weathersby:
Yes. Yes. I wish I could go back and thank every woman and every baby who went through that so that my three babies could be alive today.
Molly Sherwood:
Yes.
Bethany Weathersby:
So we appreciate everyone who has sacrificed for these incredible advancements.
Molly Sherwood:
Now, I want to talk about the most significant, the most, for sure, significant advancement in the prevention of HDFN. And this is also in the '60s. So in 1968, this is about five years after Lily's use of IPTs, which Dr. Moise just talked about, the first preventative for alloimmunization was launched, and that is the drug called Rhesus immune globulin. The trade name is rhogam or WinRho, and we did talk about that in its utility in our prenatal blood test episode earlier in the season. But this breakthrough helped women who are pregnant, who carried Rh negative blood to be able to carry Rh positive fetuses without developing anti-D, without becoming alloimmunized to the D antigen. And so the sensitization rates for anti-D just plummeted in developed countries. And it became more widely available. It's now completely universally utilized in developed countries. That's not necessarily the case in undeveloped countries, which as an aside, it's even more critical there where treatment is not possible. So the only option is prevention.
Bethany Weathersby:
Right. Yeah.
Molly Sherwood:
So the number declined dramatically of cases. That's what made this disease a rare disease, truthfully.
Bethany Weathersby:
Wow.
Molly Sherwood:
But advancements, of course, we hope are still coming. There's no preventative medications for other antigens. Any of Bethany, our antigens that we have, it cannot prevent them. So alloimmunization still continues today to those, and of course, in cases where rhogam was not administered.
Bethany Weathersby:
Yes. And I just wanted to point out that anti-D is the most common antibody, and that is why I guess they focused on that one.
Molly Sherwood:
Yes, definitely.
Bethany Weathersby:
Well, I don't really know why I'm guessing that's why they developed that for anti-D.
Molly Sherwood:
Yeah, makes sense to me. It was definitely the most reactive antibody.
Bethany Weathersby:
Yes.
Molly Sherwood:
Okay, the next big advancement came in the 1990s. So in 1997, it was discovered that fetal DNA floats around in the mother's plasma. And so that in theory allows for you to do a blood draw on the mom and learn information about the baby's DNA. So just one year after that, cell-free fetal DNA, we call it cffDNA, was being used to check the D antigen status of the baby just by testing the mother's blood. And that is still used today, but still being developed. So today, there are some countries that can do the same technology to test for the Kell, D, C, and E antigen status just by the blood draw on the mom. And most of those facilities are in Europe, but blood can still be drawn from anywhere in the world and shipped there. And we talk more about cffDNA testing in that prenatal blood test episode also. But that's something we champion a lot nowadays in our patients that we talk to, to see if they can gain access to those tests and avoid an amniocentesis to figure out their baby's antigen status.
Bethany Weathersby:
Yes, absolutely. I had it in my last two pregnancies. We drew blood, shipped it over to the Netherlands and had it tested. And that's how I knew that my babies were Kell positive at, I think, 14 weeks. It was great.
Molly Sherwood:
That is awesome, not awesome that they were Kell positive.
Bethany Weathersby:
Yes. Yeah, not a great result, but it was so nice to know early, "Okay, we need to really, really up our game here."
Molly Sherwood:
Right. And then one more I want to talk about. In 2003, Trevett at al, does that ring a bell to anybody? Dr. Trevett? He's on our medical advisory board too. He found that the maternal... Sorry. He found that the maternal administration of phenobarbital reduces the need for exchange transfusion in babies after birth in babies with HDFN. So this drug can help mature the baby's liver so that the baby can better process higher levels of bilirubin after birth. So that's still used today as a treatment while the mom is still carrying the baby before the baby is born in hopes of strengthening the baby's response to their disease after birth.
Bethany Weathersby:
Yes. And I also benefited, my babies benefited from phenobarbital in two of my pregnancies. The two babies who had the phenobarbital through me in utero before birth, they did not need any NICU time.
Molly Sherwood:
Wow.
Bethany Weathersby:
After they were born, even though I had severe disease, and I think that phenobarbital really played a role in that.
Molly Sherwood:
And was that Dr. Trevett who gave you that?
Bethany Weathersby:
It was.
Molly Sherwood:
That's so cool.
Bethany Weathersby:
It was. Isn't that crazy?
Molly Sherwood:
That is so cool.
Bethany Weathersby:
Yeah. When I met him for the first time during a preconception appointment, and I just was interviewing him, I guess, I said, "I just want to thank you for this development of this phenobarbital because..." Well, actually, it had been used before I met him with my daughter, Nora. And I just said, "That discovery of yours really improved my baby's health. Thank you for that." So yeah.
Molly Sherwood:
All right. Let's see. So just two years after that, in 2005, Kriplani developed the first use of IVIG, intravenous immune globulin, on a fetus in utero for Rh disease as well. And that's now used in addition to, or sometimes separately from plasmapheresis in prevention of severe... Well, not even... It's not really for prevention. It's actually just to delay the onset of severe disease in utero. By 2009, this is 400 years after the first suspected cases of HDFN were reported, we now have several methods to test for the disease, to lower titers, to help the fetus in utero, and to treat issues in the newborn after they're born. Thank gosh.
Bethany Weathersby:
Yes. Oh, my goodness.
Molly Sherwood:
I know.
Bethany Weathersby:
And most of that happened just in the past few decades, right?
Molly Sherwood:
Yes.
Bethany Weathersby:
I mean, that's amazing.
Molly Sherwood:
That's true. Yeah, that all really happened since the '60s.
Bethany Weathersby:
Yes. By the way, if anyone wants to really go down a rabbit hole...
Molly Sherwood:
Yes, please.
Bethany Weathersby:
... when we're talking about history and HDFN, look up Henry VIII and the Kell antigen. A lot of people think that Henry VIII had the Kell antigen, and that is what was happening with his babies dying in utero and shortly after birth, was HDFN. But who knows?
Molly Sherwood:
Wow.
Bethany Weathersby:
Yeah.
Molly Sherwood:
We'll never know, but maybe our next research study for the foundation could just exhume him and let's see if we can run his DNA and...
Bethany Weathersby:
That would be a practical way to use our yeah, resources.
Molly Sherwood:
Yeah, definitely. Yeah, speaking of research and stuff, let's talk about the state of alloimmunization and HDFN today now. Do you want to take about that, Bethany?
Bethany Weathersby:
Yes. Sure. And this was a weird one, right, Molly? I felt like.
Molly Sherwood:
Yeah. We really struggled with how to talk about this actually because I think you and I have mixed feelings about the state of treatment for this disease, right?
Bethany Weathersby:
Absolutely. Absolutely. I feel like there are extremes here, extreme care. There's a wide spectrum. But today, developed countries, like we said, are reaping the benefits of all of these amazing innovations that we just mentioned. So this includes the MCA scans to screen noninvasively for fetal anemia, and then the intrauterine blood transfusions, and the preventative treatments, and of course, the Rh immune globulin, close monitoring and intervention, and there's treatment after birth. So there are highly specialized centers around the globe who report high fetal survival rates from about 97 to 98%. And this is with the best care. So that's amazing. If you look at where it started. And we know in the literature and in our lived experience that survival rates like these are possible, I mean, in my lived experience with my children, and I've been told I have the worst case scenario and I have three healthy children.
So there's another side though, and we want to give you an accurate glimpse into our world of day-to-day patient experiences and support and have a little soapbox moment, I guess. So while these technologies are the established standard of care, we don't actually see the standard practiced consistently. And that's what is so difficult about this disease. And I know that it's rare. So that plays into this a lot. Even in the US and other developed countries, when a patient is diagnosed, she really has no idea what level of care she's going to receive. I mean, she could receive care that looked like the 1800s. That is not an exaggeration. Or she could receive care that's phenomenal, and her baby, which there's a great outcome with the right treatment and monitoring.
And that also puts so much strain on the patient. It's just like, "I don't really know if I'm receiving the right care or if I'm going to," and that's scary. For me personally, I was diagnosed with HDFN at the beginning of 2013. And my OB, who I love, by the way, told me that I would need to have amniocentesis every week to check for fetal anemia for the rest of my pregnancy. Okay, so when was that last used?
Molly Sherwood:
Wow.
Bethany Weathersby:
I mean, how many decades old was that?
Molly Sherwood:
Oh, my gosh, 60-year-old information.
Bethany Weathersby:
Right. This is what I'm talking about is just, I guess it takes a long time for some of these discoveries to trickle down through the actual care for the patients, for some reason. I don't really understand why. And then other patients are told, "There's no hope because you have Kell. So your baby will die. So you should definitely terminate," or whatever. Because, what, centuries ago, that was the diagnosis.
Molly Sherwood:
Sure.
Bethany Weathersby:
Is just, "There's nothing we can do." But here we are, 2022. We are here. And it's a treatable disease now, right?
Molly Sherwood:
Yeah. Yes, it is. So we're really lucky in this one sense that there actually are treatments. With good care, babies will live. So that's wonderful. That's not the case for many rare diseases. So we're very lucky in that sense. Now, we just need to get it out there.
Bethany Weathersby:
Yeah. So we wanted to... We have the benefit of interacting with lots of patients, wonderful, wonderful women who share their stories. And so we see this wide variety of experiences around the globe. And so we wanted to give our listeners a sense of what we regularly see in our advocacy work. And we took a look through our own patient support group and decided that we will take turns providing some excerpts posted from the women just in this past month. And each of these women has given her consent for her excerpt to be anonymously shared here.
Molly Sherwood:
Cool.
Bethany Weathersby:
So they are totally on board with this. And let's just go for it. All right.
Molly Sherwood:
Yes. All right. You first.
Bethany Weathersby:
So here's the first excerpt: "My OB at my appointment today said that we need to think about termination if the baby's blood comes back as Kell positive. My OB said this is an extremely high risk pregnancy and we need to prepare ourselves for termination or go through the journey to only lose the baby later on, or have a severely disabled baby. I feel like all of our hope has been shattered."
Molly Sherwood:
Wow. That was only three weeks ago. I remember that. A lot of us had thoughts and encouragement for her. Thank gosh, I'm very happy that she received some good feedback.
Bethany Weathersby:
Yes. Yeah.
Molly Sherwood:
All right, here's the next one: "Thank you so much to everyone who responded in regards to the wrong test being ordered yesterday for my husband's antigen results." That's common, by the way. Happens all the time. "Your help means more than I could ever convey. Ladies, I'm trying to keep calm and clearheaded as I think about everything, but I'm admittedly feeling disheartened by the things that keep falling through the cracks."
Bethany Weathersby:
So many things fall through the cracks.
Molly Sherwood:
Yes. All right. Your turn.
Bethany Weathersby:
Okay, here's the next one: "I'm feeling like we're heading for our first IUT. It makes me a bit anxious. My last pregnancy, I wasn't being monitored properly and we found severe anemia two days shy of 23 weeks. We did one IUT, but the baby passed sometime after the IUT, but before the next morning's ultrasound. I don't really have a question to ask the group. I just needed to vent some anxiety because you all are the only ones who get what this is like."
Molly Sherwood:
Wow, I'm going to tear up. I don't know if I'm going to get through these.
Bethany Weathersby:
Oh, no.
Molly Sherwood:
That's a sentiment that is shared of a lot of people in this group, is just feeling alone and confused, and they don't exactly know what they need, but they just feel some compassion from other women who understand. Okay, here's one more we want to put in here: "I just found out we are expecting Again. I am anti-D and terrified," in all caps. "My last pregnancy," and I cut this to be a little bit shorter for continuity, "I felt like my doctors were totally inadequate with my care. They didn't test often enough. I felt like I was chastised for asking for more and also questioning what would happen in the event of elevated numbers, et cetera. They even did an amnio on me without any pain medications. It was the worst experience I've ever had with pregnancy care. There are only two MFMs in town, and they were supposed to be the more equipped and experienced ones. I can't afford to travel out of state for specialized care. We honestly don't know if we can even go through with this." And that woman, the baby in that last pregnancy she was talking about, also passed.
Bethany Weathersby:
So sad.
Molly Sherwood:
And this is literally... I mean, Bethany, weren't these in the last... We made sure to only pull things from the last month. This is just a very small snippet.
Bethany Weathersby:
Yes. Yes. And we just heard this morning of another baby who passed away. The right care was not given in that case and it's heartbreaking.
Molly Sherwood:
It is.
Bethany Weathersby:
It really is.
Molly Sherwood:
Yeah. I hope that in the future, we can have a better way through our research and getting things out there to demonstrate the true patient experience, but I think this was a good attempt at least with the information that we do have to share some of this world.
Bethany Weathersby:
Yeah. Sometimes we do see wonderful things too. Like I said, there's a wide spectrum. We see great things happen when patients are enabled to advocate for themselves. And there are a lot of posts in our group about smooth and successful IUTs and really good post-birth monitoring. We have some amazing doctors, truly, who provide incredible care. And here are a couple examples. So listen to these two excerpts that just came in the past week or so.
Molly Sherwood:
Yeah. Okay. I want to say this one, but this one, she talked about her location. So I redacted that. So it might sound a little disjointed. "I have done all the research I can do at this moment because it seems to put me in a low place. But after hearing Bethany's story, I had my charts sent to..." She had her charts sent somewhere else to see a different doctor. "I am grateful for the support on this page and have read the majority of your posts, and will keep you and your family in my thoughts and prayers. I don't even know what questions to ask at this point, but just appreciate knowing that you guys are here and that we aren't alone."
Bethany Weathersby:
So wonderful. Okay, and here's the second one: "I ended up getting the Allo Hope Foundation's provider handbook professionally printed at Kinko's and created a cover page from their website, and left it with a thank you note for all of their help with the doctor. Not only did the doctor apologize for feeling that he needed to counsel us on the condition, but he also thanked me in an extremely kind and genuine way for bringing the info in."
Molly Sherwood:
That's awesome.
Bethany Weathersby:
It is. Wonderful patients doing this advocacy work and educating themselves, speaking up for the right treatment and doing the hard things, and then the doctors too.
Molly Sherwood:
Yeah, and it sounds like that doctor was wonderfully receptive. How awesome.
Bethany Weathersby:
Yes. Yeah.
Molly Sherwood:
Let's also point out all of those excerpts were from developed countries. Let's just briefly touch on the whole globe. Developing countries do not have consistent or sometimes any access to rhogam like we talked about. And in most cases, no treatment options for the disease. There's been some cool global analyses done about the impact of having no access to rhogam in poor regions, mostly in sub-Saharan Africa and East Asia. And so this one study found that a lack of rhogam alone results in 114,000 avoidable deaths worldwide every year.
Bethany Weathersby:
Wow.
Molly Sherwood:
And access to care, once you are sensitized, is very poor in these countries. And in some areas, the inability to carry live babies comes with a devastating social stigma and causes families to fall apart. I wish we had answers right now for the whole world, but in the absence of that, we will just try to amplify these experiences and partner with other global organizations to help.
Bethany Weathersby:
Yes.
Molly Sherwood:
Where do we go from here?
Bethany Weathersby:
Sorry.
Molly Sherwood:
This was supposed to be encouraging.
Bethany Weathersby:
So depressed.
Molly Sherwood:
I know.
Bethany Weathersby:
No, no, no. This is what it's like. This is today.
Molly Sherwood:
I know. It's a mixed bag. It's a mixed bag. We're so lucky that the stuff exists. There are options. Thank gosh. Yes.
Bethany Weathersby:
Right. We have so many amazing researchers and clinicians to thank for the state of care today, and we are hopeful that it's only going to get better from here. So let's head into the future now. We actually asked Dr. Moise what he thinks the future holds for treatment of HDFN. Let's hear that.
Dr. Ken Moise:
Where are we going to go? I'm hoping that before I retire, that we have a drug that can block the placenta and stop the bad antibody from crossing, and that nobody really needs to learn how to do these procedures. I mean, if you think ahead, I think we'll think back on this and go, "So you did what? You used to stick a needle in the cord and push blood into a baby? The baby wasn't at fault. It just happened to be the wrong blood type. Why didn't you treat this medically? Why didn't you block the antibody?" "Well, why didn't we think of that?" That's probably smart, right?
I think we're on the verge of that. I really do. I think we'll be treating this disease medically in the future, and we'll all laugh about these great stories about how people did procedures on babies. And we got away with it most of the time, and we were successful a great majority of the time, but it'll be historical. We'll look back and go, "That's all we had in the day." Just like Lilly had paper clips to put on the belly. That's all he had. And he made do with what he had and did pretty good with it. He saved a lot of babies. It's been a ride. It's been a real ride to watch a change, but we have a ways to go, but we're getting there. We're getting there.
Bethany Weathersby:
That makes me very thankful to have had my babies in the past few years, rather than two decades ago.
Dr. Ken Moise:
Exactly.
Bethany Weathersby:
That would've been a disaster. So I'm also very encouraged about the possible new treatment in the future because I have three, possibly four Kell positive sons. And so I think about that often, what will it look like if they do have to deal with this disease with their own wives and babies? I feel really encouraged about the possibility of intervention-free pregnancies for us in the future.
Dr. Ken Moise:
So your sons make up a small percentage of the population, 8%. They're probably going to have Kell negative wives. And if their wives get sensitized, they will be like their mother, having to deal with a pregnancy with problems. So you're right. That is a possibility. But hopefully, by that generation, we'll have a standard treatment that people grab off the shelf and treat the pregnancies with.
Molly Sherwood:
That is so cool to hear him say that. And also, let's read between the lines there. If he is admitting that he was around during development of MCA scans, he must not be terribly far away from retirement. So if he thinks that a drug like this will exist before his retirement, then that is not terribly far in the future, even though I don't ever want him to retire, of course.
Bethany Weathersby:
I know. Yeah. He just needs to work forever.
Molly Sherwood:
I know. Could he please? That would be wonderful. And 2019 did bring the development of a new drug called nipocalimab. It's a monoclonal antibody that does block maternal antibodies from crossing the placenta. And there are studies going on right now in pregnant women who have previously given birth to a severely affected fetus. And this is as of the time of this recording, 2022, 2023. So things can change in clinical trials. Of course, we will just include a link to the clinical trials page for the drug, and then you can track the status in real time at the time that you listen to this.
Bethany Weathersby:
Yes. And we also as a foundation share Dr. Moise's dream to have a therapy available one day that makes the need for intense intervention for HDFN obsolete. That would be amazing. We also have some other dreams for the near future of treatment of this disease that we're working hard to accomplish as a community. And this was also why the foundation was created in the first place, is the wish that we have for every woman in the world to receive the right care during her alloimmunized pregnancy. And I would personally love every patient to receive the treatment and care that I received in my last three pregnancies and the same beautiful result of healthy living babies at the end.
And we want to support patients through their journeys. Here's what we are trying to do to achieve that goal: Providing more resources for both patients and providers that are evidence-based and widely distributed and accepted by the community, conducting our own patient-centered research to share a true patient representation of standard care and the psychosocial impact of this disease on mothers that Molly and I were talking about earlier. We want to show what it's really like today. We want to advise on large private research programs to help amplify the patient voice and further examine comparative effectiveness for treatments for this disease, offering referrals to expert practitioners, yes, offering mental health support to patients. Overall, we just want to make living babies and emotionally supported mothers the standard of care around the world in every single country.
Molly Sherwood:
That's it. That's the future.
Bethany Weathersby:
We're going there.
Molly Sherwood:
If you, your partner or someone close to you has antibodies in their pregnancy, we are here for you. We have a great resource library on our website at allohopefoundation.org. That's allohopefoundation.org.
Bethany Weathersby:
Thanks for listening. Oh, my gosh. Okay, let me do it again. Thanks for listening.
Molly Sherwood:
The Allo Podcast is a production of the Allo Hope Foundation. It was researched and written by Bethany Weathersby and me, Molly Sherwood. It is produced and edited by CJ Housh and Eric Hurst of Media Club. The Allo Podcast is sponsored by Janssen Pharmaceutical Companies of Johnson & Johnson.