Testing is the first step toward having a safe and healthy HDFN baby. This episode covers the importance of early tests that can determine how severely your baby will be affected by your antibodies. We include information about new tests, Rhogam, and how you can donate plasma to help other expectant mothers determine the antigen status of their babies.
Testing is the first step toward having a safe and healthy HDFN baby. This episode covers the importance of early tests that can determine how severely your baby will be affected by your antibodies. We include information about new tests, Rhogam, and how you can donate plasma to help other expectant mothers determine the antigen status of their babies.
Episode themes:
Plasma Donation: Southern Blood Services https://southernbloodservices.com/
For information on donating to create test kits email msertell@southernbloodservices.com
Terminology used in this episode:
Cell Free Fetal DNA (cffDNA) information https://allohopefoundation.org/library/cffdna/
cffDNA direct from Sanquin Laboratories https://www.sanquin.org/products-and-services/diagnostics/non-invasive-fetal-blood-group-genotyping
Allo Hope Terminology Library https://allohopefoundation.org/library/terminology/
For more on tests during pregnancy, see our prenatal testing guide at https://allohopefoundation.org/library/prenatal-testing/
Guests: Dr. Thomas Trevett http://www.georgiaperinatal.com/dr-trevett/
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.
Molly Sherwood:
The information shared on The Allo Podcast is not intended as medical advice. Your medical care decisions should be made in consultation with your physician who is familiar with your specific case.
Bethany Weathersby:
Hi, welcome to The Allo Podcast from the Allo Hope Foundation. I'm Bethany Weathersby.
Molly Sherwood:
And I'm Molly Sherwood.
Bethany Weathersby:
And-
Molly Sherwood:
We're going to smash this episode today.
Bethany Weathersby:
This is the third time we are recording this episode, it's going to be incredible.
Molly Sherwood:
Yeah. We had some technical... Bethany, before, you are having a hard time being happy. "It's going to be incredible."
Bethany Weathersby:
Okay.
Molly Sherwood:
I mean, it's hard to be excited because we already recorded this twice, but the first time we did it, we weren't happy with it. The second time we did it, only your portion uploaded. So it was just Bethany talking to herself.
Bethany Weathersby:
Right, yes, we had technical difficulties. We feel like it's a little bit cursed on our end, but hopefully this is the best take right here.
Molly Sherwood:
Yeah, that's true. This is either going to be the best ever or it's going to be just a total disaster because it's cursed.
Bethany Weathersby:
Whatever it is, this is the last time doing this.
Molly Sherwood:
Yeah, take it or leave it. This is it.
Bethany Weathersby:
Honestly, it's such an important episode. The topic is so crucial to receiving the right treatment and having a safe and healthy pregnancy. So that's why we are dedicated to it enough to do it three times.
Molly Sherwood:
I know. If it weren't really important, we definitely would've trashed it and just moved on.
Bethany Weathersby:
Yeah, absolutely. Okay. So what are we talking about? This episode, we're covering prenatal blood tests, which might not sound the most exciting topic, but these tests are actually super important for Allo immunized patients. Blood tests are the first line of defense against this disease. It was a blood test that let you know in the first place that you had these antibodies.
Molly Sherwood:
And that's true. What's unique about our disease is our babies could be affected, but there's no way externally, we would ever know. We can't tell in our bodies, so we totally depend on blood tests before moving to further monitoring too. And we're not just going to cover tests for the mother today. We also have to include tests for the baby and the father, which causes a lot of confusion. Hopefully, we can help clarify why it's important and why it's necessary.
Bethany Weathersby:
Let's start at the very beginning of the pregnancy with the mother's blood work. First, you have the initial blood test called an antibody screen and that shows you that you have these red cell antibodies. Does this always show which type of antibody the woman has, Molly?
Molly Sherwood:
It doesn't show right away. What happens is this is in the US and in developed countries, the standard of care early in your pregnancy is to have your first trimester blood work. That includes, for every woman, this antibody screen. If it shows up positive, you would get a positive screen and then you need to do a follow up test of that blood called the antibody ID. That identifies the actual antibody that you have. Then the next blood test, as soon as you have that information, is your titer. The titer just means the amount of antibodies in the mama's blood.
Bethany Weathersby:
Right. Then really quick, I just wanted to say that sometimes, when they're telling the patient about this positive antibody screen, they do go ahead and say, "This is the antibody that you tested positive for." Then sometimes, they don't. Sometimes, they give it all to you right up front. You tested positive, this is the type of antibody you have, and this is your titer. It's kind of confusing. We don't know what these newly diagnosed patients are being told-
Molly Sherwood:
That's true.
Bethany Weathersby:
... because it's all different.
Molly Sherwood:
It seems like it depends on the lab. Some labs will quickly get a positive, and then ID and titer, and you have all the information right there, or they get a positive, and they have to send it off for ID and titer, and then you have to wait several days sometimes.
Bethany Weathersby:
However you get there, these are the things you need to get, the type of antibody and the titer. So the titers don't actually tell us anything about how the baby is doing.
Molly Sherwood:
Yeah. They give us sort of a general idea about how much risk the baby could be facing. So titers are shared in multiples. So it goes from two low to titer, one, two, four, eight, 16, 32, and so on, into the thousands. But what the important threshold is to know what we call critical titers, which is the threshold at which more monitoring is necessary. For all antibodies, with the exception of Kell, the critical titer is 16. For Kell, it is four, but some centers, even just any titer prompts further monitoring, because Kell can be more aggressive than others.
Bethany Weathersby:
Yeah, I have Kell and the titer is in the thousands, but if mine was below critical, I would definitely be asking for some regular MCA Doppler scans, just to be careful and check for fetal anemia. Even though titers can't tell us how the baby is doing, they do give us some really important information, especially super high titers are telling us that there's a much higher possibility the baby will be affected by the mother's antibodies, because there are so many antibodies there in the mother's blood.
Bethany Weathersby:
If your titer is in the hundreds or thousands, it's a good idea to talk to your provider about preventative treatments, like plasmapheresis and IVIG, and maybe start MCA Doppler scans earlier. My are in the thousands and for the babies that received the correct care and survived, we started MCA Doppler scans at 15 weeks and 14 weeks actually. I used preventative treatments, plasmapheresis and IVIG, to delay the onset of fetal anemia. So if you do have super high titers, that's something to look into with your physician.
Molly Sherwood:
When did you start your plasmapheresis and IVIG?
Bethany Weathersby:
Yes, I started the plasmapheresis around, I think, nine or 10 weeks. And then the IVIG was between 10 and 12 weeks.
Molly Sherwood:
We definitely will talk about it in the severe disease episode, but I just want to say it because I think it's important for women to be aware of that timeline about why it's critical to figure out your titer very early on, because should it be really high, then that option may need to be explored right away. Finding out your titer and antibody, really, as soon as you find out you're pregnant, I would say is a good recommendation, do you think?
Bethany Weathersby:
Yes. Yeah, absolutely. Because if you do need these early preventative treatments, it's good to get started setting those up right away. So what if your titers are below critical? I don't have any experience with that, unfortunately, but if you do have titers below the critical threshold, how often do those titers need to be monitored?
Molly Sherwood:
So the recommendation now is to have your titers checked every four weeks until your third trimester, and then every two weeks thereafter, because your blood circulation is increasing a ton while you're getting super, super pregnant. Your titers can really fluctuate, especially toward the end. So the recommendation is every four weeks until your third trimester and then every two weeks until 36 weeks, just your last month of pregnancy.
Molly Sherwood:
Then weekly at that point until delivery. We do talk about delivery and titers in more of episodes too of course, because they're so important and we get lots of questions on them, but delivery for our population of women, even in a non-critical titer, assuming the baby is assumed to be affected, is a 37 to 38 week induction.
Bethany Weathersby:
Or if you don't know if the baby's affected, correct.
Molly Sherwood:
Yeah. Right. Yes, that's true. If you don't know or if you are certain, yeah, then 37 to 38 weeks.
Bethany Weathersby:
Okay. Okay. So now let's talk about the father's blood tests. A lot of people wonder why does that matter? There's a pregnant mom and a baby in utero, what does the dad have to do with anything here? But his blood actually is really important to this equation and to the monitoring choices. After the antibody screen and titer for the mother, the baby's father is usually tested next. To explain why the dad's blood tests are important, we just have to look at two important things. I just said important a million times, to explain why-
Molly Sherwood:
It's important.
Bethany Weathersby:
All right. So why are the dad's blood tests important? Before we go into that, we have to look at antigens and antibodies. We did discuss those things in great detail in the first episode, the HDFN101 episode, but basically, the mother's antibodies... So the mother has the antibodies and the baby's father has the antigens. That's what we're looking at here. The mother's antibodies are specifically designed to destroy a certain blood type with a certain antigen on it.
Bethany Weathersby:
The antigen is inherited from the father, just like a blood type. We need to find out if that baby has the antigen that the mother's antibodies are going to be trying to attack, if that makes sense. Because it's inherited, we are looking at the father's blood to see if he has that antigen, because if he does not have that antigen, then the baby can't, because it's inherited from the father. A quick reminder that antibodies do the attacking, antigens get attacked.
Molly Sherwood:
Yeah. The baby can only be affected by the mom's antibodies if the baby has the antigen that matches the mom's antibodies, that's why we need to know the dad's antigen status. The dad needs to get a test called an antigen phenotype, write that down. It's not infrequent that the father gets an antibody screen instead, we've seen that happen. The dad does not need the antibody test, but we're looking actually for their antigen status specifically for the corresponding antigen.
Molly Sherwood:
So for example, if you have anti-E, then we need to find out the dad's antigen phenotype for E. The blood test tells us not only does he have the antigen, yes or no, it should tell us if he's homozygous or heterozygous. We explain what that means in the 101 episode. But essentially, the way it matters to us is that homozygous means that the baby has a 100% chance of inheriting the antigen. We know the going to be affected in that case.
Molly Sherwood:
Heterozygous means there's a 50% chance the baby will inherit the antigen. Of course, if the father is negative for the antigen, which can happen, especially if the woman has developed her antibodies in the case of a blood transfusion, that means the baby has a 0% chance. Totally in the clear, no monitoring needed, non-affected baby.
Bethany Weathersby:
Molly, was your husband homozygous or heterozygous or negative for the antigens?
Molly Sherwood:
I have two antibodies. I have anti-S and anti-E, and he's heterozygous for the S, meaning our kids have a 50% chance of inheriting the S antigen, which my antibodies attack. He is homozygous for E, meaning all of our babies inherit the E antigen.
Bethany Weathersby:
Yeah. Okay.
Molly Sherwood:
Josh is heterozygous, right?
Bethany Weathersby:
Yes. So I have anti-Kell and Josh is heterozygous for the Kell antigen. So what if the dad is heterozygous and there's a 50% chance the baby has inherited the antigen? How do we know if the baby is antigen positive or negative? Let's go into that next blood test.
Molly Sherwood:
This is where it can get tricky because there's a few options here. The one that used to be recommended because it was the only thing available is doing an amniocentesis. You've had an amnio before.
Bethany Weathersby:
Yes.
Molly Sherwood:
How does that work?
Bethany Weathersby:
They just stick a needle through the mom's uterus and draw out a little bit of the amniotic fluid. That's the fluid surrounding the baby. And then they can test the fluid to find out the baby's antigen status. But it does come with some risks. Risks are rare, but they're possible. Well, especially with our condition, one of the risks is that it could possibly cause the mother's antibody titer to go up, which you really don't want.
Molly Sherwood:
Yeah, that's true. That's why subject matter experts in our disease now try to avoid doing amnio's. It used to be very common that it was just the next step, but even for me, my doctors gave me the choice and said, "You can do it if you want, but we're not going to push it." I ended up not doing an amnio. So option one is an amnio, option two is just monitor the baby as if they're antigen positive, just assume they're positive, and do your monitoring the way that you should. Then should the baby start to show signs of anemia, like they may need an intrauterine transfusion, then you confirm their blood type at that time.
Bethany Weathersby:
Yes. Okay. The signs of anemia is like we're talking about the MoM?
Molly Sherwood:
Yeah. We're talking about the MCA Doppler scan, the ultrasound scan, which will give us the MoM value. If we get a high MoM of 1.5 or approaching 1.5, then that's when it would be time to figure out once and for all the baby's antigen status. Then the third choice is something that is newer to the US. It's called cell free fetal DNA testing.
Molly Sherwood:
The way it works is it's actually just a blood draw on the mom. This is the least invasive option and it collects circulating fetal DNA from your own circulation. Then it can type the baby's blood. This is actually only available for DK, for Kell, E and little C, right Bethany?
Bethany Weathersby:
Yes. I think big C too.
Molly Sherwood:
Oh, okay. And big C.
Bethany Weathersby:
Yes.
Molly Sherwood:
But it's currently very difficult to access in the US. We will post in the show notes how you can do it. Right now, the main lab that does it is in the Netherlands. It would need to be lot of logistics, but it can be done. Also, this test has a 99% sensitivity and specificity. It's amazing.
Bethany Weathersby:
It does sound a little bit difficult to send your blood over to Amsterdam for testing, but it really is not that hard. It really is not and it's so worth it, in my opinion, to have this critical information about your baby's antigen status and not pose any extra risks to that baby in utero. So I actually talked to Dr. Trevett about amniocentesis and their risks versus cell free fetal DNA tests. So let's hear what he had to say about that.
Bethany Weathersby:
When I met you for the first time for the preconception appointment, before I got pregnant with my son, Callum, I asked you if you used the cell free fetal DNA test, and you said you hadn't heard of it for Kell, but you were totally willing to look into it and use it if it seemed reliable and safe. We did go on to use that test with my next two pregnancies and I loved it. So do you use that test for all of your patients now? And if so, what made you decide to use that test instead of the amniocentesis?
Dr. Thomas Trevett:
Well, amnio's are inherently risky. Anytime we put a needle into the amniotic sac, we're risking the potential of a miscarriage. That risk is somewhere between one in 300 and one in 800. But the other issue with an amnio in a mom who is potentially sensitized to a certain antigen is that we can actually dramatically worsen the antibody response by causing a mixture of mom's blood and baby's blood.
Dr. Thomas Trevett:
So these cell free fetal DNA options are invaluable at this point, in my opinion. They're available for the D antigen, the Kell antigen, as well as the C and the E antigen through the same lab in the Netherlands. So I use those all the time now for any patient who has immunization or is at risk.
Bethany Weathersby:
I have had four sensitized pregnancies. In the first one, I didn't choose to have the amniocentesis. So we didn't know her antigen status and that was pretty stressful. Then we did not receive the right care and she passed away. So with my next baby, I did the amniocentesis and with my two last pregnancies, I did have the cell free fetal DNA test.
Bethany Weathersby:
It was by far the best experience of all those, because we could find out earlier, we did the test at 14 weeks, and it was just a simple blood draw for me. Then we found out about a week later that the babies were antigen positive and we could move on with our treatment plan after that. So I guess I found out about 15 weeks the baby's antigen status, no extra risk to the baby.
Bethany Weathersby:
Even though it wasn't the best test result, I really wanted a negative baby, but I highly recommend the cell fetal DNA test if possible. With those three babies, one baby had the amnio, the other two had the cell free fetal DNA test, despite titers, the baby with the amnio was affected by my antibodies, the earliest of those three.
Molly Sherwood:
Interesting.
Bethany Weathersby:
I don't know if that's connected, although the titers were pretty similar with all three, but she was the earliest affected. And so I always wonder if that was because I had the amniocentesis and that sped up the onset of fetal anemia. I don't know.
Molly Sherwood:
Interesting. Yeah.
Bethany Weathersby:
Yeah.
Molly Sherwood:
We need to publish a case series on you, just on your pregnancies.
Bethany Weathersby:
Yeah. Oh my gosh.
Molly Sherwood:
Before I switch our train of thought, I'm going to recap really quickly, the blood tests we're talking about. So this is the stuff that you need to do as soon as you find out you're pregnant and if you already know you have antibodies, then right away, you'll want to get your titer and your antibody ID. You probably already know your ID by then, but if you just got pregnant, you know you have antibodies, find out your titer right away.
Molly Sherwood:
If you don't know, then you'll probably find out on your own during your first trimester blood screen. At that time, you'll want to learn your antibody ID and your antibody titer. Then we talked about what a critical titer is, which is 16 for all antibodies, except four for Kell. At that point, you'll move on to different types of monitoring, which we talk about in other episodes. Then the next sort of blood test group to consider is figuring out the baby's antigen status.
Molly Sherwood:
That's what we do by having the antigen phenotype test run on the dad. If that comes back to be heterozygous, meaning the baby has a 50/50% chance of inheriting the antigen that your antibodies are going to attack, then we just talked about those options for the baby to figure out their antigen status. We talked about amniocentesis, we talked about monitoring as if the baby was positive, and we talked about the cell free fetal DNA testing.
Bethany Weathersby:
Yes. Just a quick reminder, the antigen status of the baby is so important because if the baby is antigen negative, the mother's antibodies cannot affect the baby in utero. That baby is 100% safe from those antibodies. That's why it's so important to know, because man, what a relief. I've never had-
Molly Sherwood:
You're Like, "That must be nice."
Bethany Weathersby:
... a negative antigen test result, but I can imagine, and I know other women, it's just such a relief to get that test result and know, "Okay, my baby is safe. I don't have to worry about my antibodies affecting the baby. And I can just now move on with a typical pregnancy."
Molly Sherwood:
Wow. Imagine.
Bethany Weathersby:
So yeah, imagine.
Molly Sherwood:
Okay. You know what else I want to talk about? I want to go back to what we were talking about the first trimester blood work, because this is a critical piece of really all pregnancies actually, is talking about rhogam. Rhogam is actually the trade name for something called RH immune globulin. Rhogam is used to prevent the development of anti-D antibodies.
Molly Sherwood:
A major goal of the first trimester blood work, in addition to figuring out if you already have antibodies is to determine your blood type. If you have a negative blood type, like O-negative, that means you do not have the D antigen. The plus or minus on your blood type is actually talking about the presence or absence of the D antigen.
Molly Sherwood:
If you have a negative blood type, that puts you at risk for developing anti-D antibodies during your pregnancy and birth. We do not want that to happen. I mean, the women in our community who are already sensitized would never wish this experience on somebody. Rhogam, ta-da, is a shot that... Sorry, I'm very happy that rhogam exists.
Bethany Weathersby:
I know, I can't imagine being able to prevent my antibodies from developing.
Molly Sherwood:
Right.
Bethany Weathersby:
That would've been amazing.
Molly Sherwood:
I know. Yes. Rhogam is a shot-
Bethany Weathersby:
It deserves a sound effect.
Molly Sherwood:
Yes.
Bethany Weathersby:
That's all I'm saying.
Molly Sherwood:
Glad I could provide.
Bethany Weathersby:
Yes. Thank you.
Molly Sherwood:
Rhogam is a shot that goes in the mother's upper thigh area. It contains a really, really small amount of RH positive proteins. They keeps your immune system from making any permanent antibodies to any blood that has the D antigen. Before rhogam, which has only been around for like 60 years, and in countries without rhogam, because some developing countries don't have consistent access or any access, the sensitization rate to anti-D is about 15 to 20% per pregnancy.
Molly Sherwood:
That means if you have a negative blood type and you don't get rhogam, then you have a 15 to 20% chance every time you're pregnant of developing anti-D. Rhogam is so critical and it's the only preventative treatment against this disease, at least to the D antigen, which is otherwise the most commonly occurring. No, in the US, the more minor antigens are more common, like ours Kell and E, since rhogam is a thing now, we see less D, thank gosh. Rhogam is critical for anybody with a negative blood type to prevent them from becoming alloimmunized.
Bethany Weathersby:
Definitely. If you have a negative blood type, ask your doctor about rhogam. I think most of the time, it's given routinely, but it can be overlooked sometimes.
Molly Sherwood:
Oh yeah. I'll just share when it needs to be administered.
Bethany Weathersby:
Sure.
Molly Sherwood:
If you do have a negative blood type, you need to get rhogam during any pregnancy bleeding and at 28 weeks pregnant and at delivery, that's when you should expect to receive rhogam. You should get it, even if you... If you have antibodies already to other antibodies that are not D, but you have a negative blood type, you still need rhogam. If you already have D antibodies, if you're already alloimmunized, rhogam will not help you, can't prevent something that already happened. So then you don't need it.
Bethany Weathersby:
Well, since we are discussing rhogam, I did want to mention a really special way patients can give back after they have experienced alloimmunization. Women with red cell antibodies can actually donate their plasma in specialty clinics. That plasma can be used to help protect other women and babies from HDFN, which is really amazing. If you have anti-D antibodies, your plasma can be used to create this RHD immune globulin that we were just talking about, which can then be used to prevent other women from developing anti-D antibodies.
Bethany Weathersby:
If you have one of the other red cell antibodies, besides anti-D, your plasma can be used to create blood typing tests, which are necessary for the safety of blood transfusions and organ donations. The blood typing tests are also used to identify red cell antibodies during pregnancy, like we were talking about the antibodies screen at the beginning of this episode. These blood typing tests are used to identify antibodies in pregnant women.
Bethany Weathersby:
After I had my babies, I realized that there is actually one of these specialty plasma collection centers right down the street from me, walking distance, it's crazy, called Southern Blood Services. I decided to donate plasma so that I could use my antibodies for good. It was a very, very dark time for me, but this was a light for me. It felt like, okay, this horrible thing that happened to me, I'm going to turn it around and use it for good, and hopefully prevent other families from experiencing this trauma.
Bethany Weathersby:
The plasma donation process takes about 45 minutes. It can safely be done twice per week. Southern Blood Services is currently looking for new donors for their RH incompatibility program and their red cell antibody program. Anti-D antibodies or any of the other red cell antibodies. If you qualify to be a donor for their red cell antibody program, Southern blood services will pay you for your transportation and hotel accommodations while you donate at one of their locations.
Bethany Weathersby:
They also compensate you for each donation, which is really nice. If you're interested in donating plasma, you can contact Martina Sertell at msertell, that's M-S-E-R-T-E-L-L@southernbloodservices.com for more information. Of course, we will include all of this information in the show notes. I think that's it, Molly. Did we cover everything?
Molly Sherwood:
I think we did. We'll never know if this was better than our last one, since we lost it, but hopefully it was.
Bethany Weathersby:
It's good enough.
Molly Sherwood:
If you or 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 allo, spelled A-L-L-O, hopefoundation.org.
Bethany Weathersby:
The Allo Podcast is a production of the Allo Hope Foundation. It was researched and written by Molly Sherwood and me, Bethany Weathersby. It's produced and edited by CJ Housh and Eric Hurst of Media Club. The Allo Podcast is sponsored by Janssen Pharmaceutical Companies of Johnson & Johnson.