#188 | Rhogam for Rh Negative Mothers: How It Works and When It Doesn't

November 23, 2022

In today's episode we discuss the problem with Rh negative blood types and how it impacts future pregnancies. We've invited Courtney, mother of three, and her midwife, Jessica, to discuss her experience as an Rh negative mother who became isoimmunized against her baby, resulting in the need for multiple in-utero blood transfusions to save her baby's life. 

Typically, women who carry the Rh negative blood type are given a blood product called Rhogam, which protects the mother from developing an auto-immune response against her future babies. In Courtney's case, Rhogam (also known as anti-D) did not work. As a result, her own body "attacked" her third baby, causing her baby to have life-threatening anemia in utero. 

The purpose of this episode is to help mothers (a) learn about the issue behind Rh negative blood types; (b) understand how Rhogam works to prevent isoimmuization; (c) know the risks associated with receiving the Rhogam injection; and (d) feel empowered by discovering that even a high-risk pregnancy, such as Courtney's, can be co-managed under midwifery care to achieve the labor and birth goals associated with a low-intervention or natural birth.

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View Episode Transcript

I'm Cynthia Overgard, owner of HypnoBirthing of Connecticut, childbirth advocate and postpartum support specialist. And I'm Trisha Ludwig, certified nurse midwife and international board certified lactation consultant. And this is the Down To Birth Podcast. Childbirth is something we're made to do. But how do we have our safest and most satisfying experience in today's medical culture? Let's dispel the myths and get down to birth.

So I'm Courtney. And I have three boys. And I'm about to share my journey through my three pregnancies dealing with isoalloimmunization, which is, which is a condition that develops when an Rh negative mother has an Rh Positive partner and the baby in utero also as a positive lead type.

Okay, I have two questions. One, when you say RH negative and Rh positive is that when there's a minus or plus after someone's blood type, so we're not talking about someone who's blood type? A, we're talking only if someone has a positive or a negative any blood type. But if it only has that Rh factor, and the second is how do you know a baby's blood type in utero?

There is you don't know unless you have specific blood typing that is done during the pregnancy, or amniocentesis would be the only other way to know prior to birth. Okay.

So Courtney, you have your very own midwife here on the show with us today to help us all understand what this Rh Positive RH negative blood type incompatibility means and what it means for your pregnancy journey, we're gonna get to hear that story of how you had to make some difficult decisions about how to be managed in subsequent pregnancies. So we are lucky enough to have Jessica here with us who it's an honor Jessica to have you on the show as a fellow Yale alumni midwife is. So can you help our community and our listeners understand what this all is?

Absolutely, thank you so much for inviting me to be here to help. Share in in Courtney's journey, it has been an incredible experience to be by her side through this process.  My name is Jessica Pipitone Stanek, I am a faculty member at the Yale School of Nursing in the nurse midwifery program. And I, this is a very common thing that many pregnant patients have to make a decision around if in fact, they are RH negative like, like Courtney was saying. So there are different blood types. There's A, B and O. And we're kind of familiar with who has those. But there's an additional blood type identifier that is an Rh factor. It's a protein on the red blood cell, which is a marker of compatibility for someone's blood to mix with another's blood. So the process of alloimmunization, which is essentially, Courtney's own body's response to a foreign antigen from her fetus from her baby, from another human, and this happens, this alloimmunization happens in blood transfusions, people who receive donated blood and also in pregnancy.

So the baby and the mother actually exchanged blood in the process because I know a baby can be born without a blood disease the mother has or an entirely different side, but they do at some point after conception exchange blood, and that's where that's the point we're talking about here.

Exactly. And that can lead to exposure into the the mother's immune system, and that could happen at various points, you know, throughout. throughout the pregnancy itself. There's different opportunities for that, but how the immune system works because it just takes that first exposure for the body to be able to recognize and then prepare and mountain attack for the second exposure, where the fetal cells then are flagged for destruction, essentially. And so if the patient is are, is Rh negative, and in Koreans case the father is Rh positive, the chances of the baby being Rh positive is either 50% or 100%, based on how many copies of the gene the father actually has. So from there in the second pregnancy, or the second exposure, I should say, these antibodies crossed the placenta allo immunization occurs and those cells that are flagged for destruction, cause they are red blood cells, and they cause fetal anemia. And that is that is the point where Courtney was being monitored with ultrasound and determine whether or not she should intervene in in order to either deliver the baby early to prevent this from continuing to happen with this own attack from her body towards her baby, or she can if the baby's very premature, you weigh the risks and the benefits and you can administer internal in utero fetal blood transfusion, which is very rare and something that was just a phenomenal feat that occurred with our maternal fetal medicine team.

Jessica, you made a reference to the second time this exchange happens? Did you mean to say or does that mean in the second pregnancy or a subsequent pregnancy only? And is there no risk to the first part in the first pregnancy with the first baby? That's the first question I have?

Yes, there's usually very little risk that first go round.

So it's non issue. If a woman plans to have one baby or it's her. It's a non potential exam when the risk is is lower. Yes.

Also, just to clarify, there's also no risk to the mother in this situation, the correct the main risk is to subsequent babies. Yeah.

Okay, because of that attack system that can be triggered. Okay. And the second question I had, that's a quick one, what is allo immunization.

So that is the process of your body forming an immune response to foreign proteins from another human. So either in blood transfusion or in pregnancy? Okay, so your body is like ready to attack someone else's blood type, essentially.

So this was not an issue with my first pregnancy. When I got pregnant, the second time, we discovered relatively early on that I had antibodies developed, or did you discover that I actually had some mental bleeding early in my pregnancy. And so at that time, we simultaneously took bloodwork to work that up, and I was given broken. So with my second pregnancy, because those two events happened simultaneously, we actually weren't sure if it was a false positive, because of the program that I had the antibodies or if it was a true interaction that had happened with my first pregnancy.

And you knew at this point that you are RH negative and your husband was Rh positive. So you knew going into your second pregnancy, that this could be an issue or we're, you know, we I found out when I had the antibodies, we then tested my husband's blood type. And we found out early on then that he was Rh positive. And he carried two of the dominant factors in his blood, which meant that all of our children in the future would be positive as well.

So there was 100% chance that any future babies this was going to be an income pellet incompatibility issue with the blood types, correct. Correct. So they monitored, they continued to monitor and my blood levels, they my blood levels started to rise. And when they got to the critical point, there's a there's a threshold that they consider critical. I started to have bi weekly ultrasounds, and during those, the middle cerebral arteries, blood vessel in the baby's brain, they measure the velocity, the speed of the blood going through that vessel, and that directly correlates with how potentially anemic that the baby may be. For my second pregnancy, that level never rose. It was never an issue, you know, we delivered as normal. Although I did deliver a little bit early, but she was not affected.

This might be a good time for us to have Jessica explain. In these in subsequent pregnancies that there is a medication that is sometimes offered to mothers called rogram, which can help prevent this incompatibility issue. You didn't mention anything about taking program was that something that was offered to you in your second pregnancy?

I did receive rhodium appropriately with my first pregnant See at 28 weeks and then again at delivery. This was something that was given because we knew that I was RH negative from the beginning with even with my first pregnancy. My second pregnancy, I did receive rogram as well, again, because we weren't sure if it was a false positive that I had the antibodies or if they were true, so we erred on the side of caution for the second pregnancy.

Right, so bro Gam is a prophylactic attempt. And to administer a blood product, it's actually a blood product. It is a human plasma, essentially, and it is from donor plasma with a high amount of these anti D which is what we're talking about in terms of the protein that's being expressed that Courtney's body is wanting to attack immunoglobulin. And what it does is it binds to any sort of any Rh positive factor that's detected in her bloodstream. The actual mechanism of action is not precisely known, sometimes it it's either it saps up all of the potential floating around Rh positive factors from her husband, right, or essentially from the baby that was donated from the husband essentially, or it down regulates her own immune response to then attack. So if you get ro Gam, then you are potentially stopping her immune system from going ahead and flagging and destroying the red blood cells within the baby in that pregnancy. So the tricky part about Courtney's pregnancy is that that didn't that was unsuccessful, unfortunately, and this is such a, the the administration program actually lower has lowered the risk in the general population from 10 to 12%. to about point one. So it in fact, is now something very, very rare. So somehow, blood mixed between the fetus and the mother between Courtney's baby and Courtney, and and there was not possibly enough rogram given that we don't really know what the cause. But despite our prophylactic efforts, it's still her body's still started to mount this response. Maybe she just has a superhuman immune system. We don't know.

Just to be clear, Courtney, you had rogram at the after the birth of your first child? Yes. Right. And then you had it again, at the same time in pregnancy with your second baby. Yes, prophylactic prevention. And Jessica, you're saying that the administration of program in these situations is basically like 99.9% effective because of how Yes, because of how specific it is and how great it is in controlling the immune response against the fetus.

And in order for it to be this effective, it does need to be given after the birth shortly after the birth of the first child to prevent that immune response from kicking in.

Anything that mothers produced, we soak it all up with the RhoGAM and hope that it just quiet same immune system for subsequent pregnancy. So then, the next Rh positive baby that comes down the pike, no one that the immune system is not ready to just launch an attack.

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So the first thing is Courtney was one the one in a thousand. For her it didn't take. Okay, so two questions. One is how did you know it didn't take for Courtney? How does a woman know?

So Courtney, had those positive antibodies show up in her blood test. And we were confused. Were like, wait a minute, how would you have that if in fact, you received the program to soak it all up? It didn't really do a great job. Where's this coming from? And so they determined that she in fact, yes, was sensitized. And from there on, it's like, there's nothing to do other than monitor for the potential severe fetal effects and that is anemia. So they were doing ultrasounds to check to see if the baby had progressive anemia. And then that, you know, the potential is is stillbirth and death. Unfortunately, if this goes unchecked if you don't deliver the baby too soon, or give the baby a transfusion inside in utero, because this severe anemia as a result of the destruction from the maternal immune system results in a syndrome called hydrops. fatalis and that that produces swelling of the liver and the spleen and the heart of the fetus and it's it's fatal. So the balance was, how premature was Courtney's baby to be there delivered at that time? Or if the risk of prematurity is is so great, and the potential to transfuse is pretty successful. And we have a team that's very, you know, capable and able of doing that really, quite successfully. And several times no doubt. Because Courtney, I think, how many transfusions did your baby end up having?

i My third was I set third son, he was you know, infected and the ultrasounds we can see the the level of velocity in the blood vessel rising. And that's when they recommend the blood transfusions. He had a total of six intra uterine blood transfusions.

Right. And that prevents that hydrops fatalis from developing essentially. So it's a life saving effort. Because there's nothing we can do to control. Courtney's immune system at that juncture, it just was on a mission to get the foreign protein and take care of it. It was doing a very good job, but unfortunately, at the consequence of the fetal prognosis, so you were still sensitized with the second baby second pregnancy, but everything went on normally baby was born full term, no intervention. And then this all in the third pregnancy started to become evident that yes, it was no longer in check your body was rejecting this pregnancy.

Okay. And that was determined by the ultrasounds. Got it.

Just to clarify, when you had explained at the beginning, that there can be this incompatibility and there's this attack response, I had assumed that that would result in miscarriage, I had no idea that could mean she's carrying the baby full term and it could result in stillbirth so that definitely is hitting home on a different level, learning that so the baby can kind of hang on throughout pregnancy, but really not make it in the end. This more serious than it even sounded in the beginning. Go ahead and I can I explain that because there's the risk of miscarriage and being affected early on is not as much because there's not as much blood from the fetus in the maternal circulation at that point. So as the baby grows, there's more volume of blood with of the baby that then could potentially be influencing or leaking into or somehow getting into the maternal system. And it's only that detection of that blood that the immune system responds to.

Okay, interesting. And I think Courtney just answered this other quick question. I was gonna say how do you know in that second pregnancy the baby you they already knew from testing you that it really didn't take? But you also said the baby was presenting as anemic? Are we talking the baby in utero the second time around, they can tell if I Baby is anemic by a scan?

Yes, when they measure the blood vessel in the baby's brain, that measurement correlates to potentially how anemic the baby is. And there's these numbers, the velocity through the brain determines whether it can see that or not. Yeah. Okay. And then my my last question, at this point, we know I'm going to have more but is for Jessica. Jessica. I'm imagining Courtney is the first one you've encountered in your career where this happened. But tell me if you have you ever had. Have you ever had a woman decline program? And if so, why? Or coordinate did you think about declining? Is there anything about rogram? That gives anyone pause? Or any Go ahead?

For me, with my first pregnancy, I, I knew that I was an Rh negative blood type. And I just knew that that was something that I should do. Now that I know, I know, I've learned so much since then, with my second pregnancy, I really learned that, you know, yes, I'm an Rh negative blood type, and my husband is positive. But there's also a chance that you could have a partner that is positive, that still carries the negative factor. So they have one positive and one negative. And there is a 5050 chance, I think Jessica mentioned this earlier, that you could in that case, have an Rh negative baby. So there are all these layers to it, you know, testing your blood type, your partner's blood type, and then you know, if your partner does have the 5050 chance, then testing the baby's blood type to see if in fact, you're looking at an Rh positive baby or RH negative baby. For me, it was never a question regarding OCAM because I was positive after that, after I learned all this, but there is a lot of information there. To look at for sure.

There is also the possibility that the woman doesn't get sensitized, correct? Doesn't it doesn't happen 100%?

Didn't we just isn't that the same point we made up to this point where she's the one in the 1000? Isn't that the same point? Or is that a different? No, she's one of 1000. With Rhogam, there is a chance that without Rhogam used to that that won't happen.

So the risk of alloimmunization happening in the subsequent pregnancy if you're not immunized with RhoGAM is upwards of 17%. So it's a it's a high risk.

Who do some women not get the shot, though. I'm not sure I'm a yes, maybe you don't end up needing it. But are there side effects? If you read the insert? Like what is it that makes some women refuse or consider not getting it?

To answer your question? Yes, I have had patients refuse Rhogam, despite the fact being RH negative. The risk of Rhogam is a theoretical risk of transmission of disease because it is a human blood product, right? But it is tested and processed and filtered to reduce and minimize that risk. But there are also other religious implications. So patients who are Jehovah's Witness, for example, who are observing that will not work just consider it and give pause to whether or not they're going to accept a human blood product. There's also allergic reactions to Rhogam possibly very rare documented anaphylaxis, which is that severe immune reaction to receiving something that your body's working hard to fight against, but also is mostly just local reaction to the at the injection site.

Is it a vaccine with adjuvants in it? Is that the hazard? Yeah, typical things. Okay. So anyone who's who might be anti-Vax? Yes, well, yeah, I don't want to label it as such. But like anyone who's going to give pause when it comes to vaccines fall into that category as well. Exactly. Whether it's the chemicals in it or Okay. Absolutely. That's a whole answer.

Good. And the conversation then usually goes to the risk of not receiving Rhogam for a subsequent pregnancy and how disastrous those fetal outcomes are for that subsequent pregnancy and what kind of consideration this person needs to really think through as a result of their action or non action.

What is the risk of loss? If they don't if they don't ever get Rhogam and they do have that second baby who is Rh positive positive, what is the risk of loss?

It's not necessarily loss, it's fetal death, and that's upwards of 17% of it. Turning into this very severe anemia that is detrimental to the life of the fetus is the 17% is the occurrence of hydrops fatalis. Is that right?

That's the occurrence of sensitization So Allison Yes, of that l immunization of that pregnancy at that time. It's it's possible it doesn't happen. Right. You know, what was the difference between loss and death? I when I said loss, I was including miscarriage, stillbirth. Do you mean death, meaning it can also be after the baby's birth? Is that why you changed the word to death?

Okay. That's convenient. Okay.

So one other thing that I have heard out there is that there are certain things that we may do in pregnancy that might increase the chances of maternal and fetal blood mixing. Do you have any thoughts on that comments on that? procedures that are done at the time of birth ultrasounds, manual extraction of placentas, I've heard, things like that, that are going to increase the chance that a mother and baby are going to have this mixing mixed blood and potential sensitization. So are there ways that we can reduce this if a woman is really is Rh negative and really is opposed for whatever reason to regram? Are there things that we can do in birth to reduce the chances of this happening?

The time of birth is the most likely chance of mixing to happen because of the just the nature of the physiologic process. But yes, I would imagine, but, but what is the consequence of not manually removing the placenta if needed, hopefully, we're doing it only at need, and then you're risking the life of the mother and not being able to control the postpartum hemorrhage. So I feel like it's all risk benefit, obviously. But we always are going to prophylaxis in the instance of someone having if or offer prophylaxis to someone who is having a miscarriage, and abortion, an ectopic pregnancy, any incidence of vaginal bleeding. During the pregnancy, we're always going to offer a bit more of an extra dose of rho gamma to hopefully capture any of that fetal blood that is, in the maternal circulation, trauma and pregnancy and impact to the belly a patient is was in a motor vehicle accident, for example, who is Rh negative would be offered an additional dose of Rhogam?

Have you ever seen any research or anecdotal evidence that frequent ultrasounds throughout pregnancy could break down some integrity between the placenta and the maternal?

I have not. But that doesn't mean it doesn't exist? I don't know.

It's an interesting thing to think about. I have not either I've heard people present that as a possibility of increasing the chances but I don't know of any evidence on it.

Right. So going into my third pregnancy, I knew from everything I had learned with my second pregnancy, what might happen, and I felt confident it I felt confident in our care team. I felt confident in the decisions we had to make. You know, once my blood levels started to rise, and I needed to have the ultrasounds, I was prepared for what was coming. It was at 24 weeks when that measurement in the baby's brain was elevated. And they recommended a transfusion and despite knowing everything that might happen, I was so prepared. It was still an emotional roller coaster. I mean, you go for the ultrasound thinking it's going to be the same outcome as it was every other time. And sure enough, I could you know, I could see it on the screen and they admit you right to the hospital. What's interesting about the transfusion is that's what they recommend doing after the blood levels rise on the ultrasound is they go in and do a intrauterine blood transfusion through the placenta, where it where the umbilical cord where it inserts into the placenta. So it's done a lot like amniocentesis is done, but they go further further in. And they can do it under local anesthetic, very low, you know, low risk that way. The interesting decision for me in this was I actually for all six transfusions that my son ended up needing, I actually opted to have an epidural from someone that had three but ultimately three births without an epidural. I chose to have six of them for these transfusions because there were other risks at play. For you know, if the baby had to be delivered prematurely, they'd have to put me under general anesthesia. My husband couldn't be there. And those risks felt heavy to me. So there was all these decisions that emotional decisions and conversations that you never want to have that that came from, from all of this, but he had his six blood transfusions, and there were six people, six blood donations prior to his birth that saved him. And he did. You know, we knew we were looking at a NICU stay delivered at 35 weeks with midwives. I think that's also the Yes, yes, a huge piece is your wanting to simultaneously have that care, albeit side by side. So that's I think the the one piece that's missing is the CO management with MFM and Free? Yes, so I was managed by the midwives and the maternal fetal medicine.

And I imagined that week by week you were having to over and over make the decision of whether the baby stays in utero another week versus giving birth preterm. How did how did you manage that? Like what were the deciding factors.

After 34 weeks, the risk of transfusion becomes greater than delivering so I knew when we approached that point, we are going to have to make a choice. Based on the way my transfusions were spread out, we made it to 35 weeks without needing another transfusion. But if we had gone on the risk of going in, because the baby's thicker, it's harder to get to the umbilical cord where it didn't starts in the placenta, the risks become greater. So I was looking at a premature delivery. But again, even in that setting, even being 35 weeks, I just like a note I really pushed through, I still wanted to deliver with the midwives I still wanted to give myself and my body a chance, you know, to do what it had done before. And not write it off, as you know, an automatic C section or, or anything. And I think the I guess the best part of the story is it was successful. So very different than my other two deliveries. But yeah, so you had a vaginal birth in the hospital with your midwives, who you had been with through the whole pregnancy and prior pregnancies. So you had that amazing benefit of the continuity of care alongside of having the advanced care of maternal fetal medicine. And that collaborative care is, ideally, the, you know, that's the optimal scenario for any high risk pregnancy.

And I think for me, there's a lot of things here, but that's one of the biggest takeaways for any other women going through this is to really advocate for yourself and your wants, and that this is a possibility to you know, still have that experience, even though you're being co managed as a high risk pregnancy important. Your other two births were vaginal births, unmedicated. Correct? Not yet. Didn't even have an IV. So you had all that good foundation in your physiology for your, your oxytocin receptors to be really receptive to my induction?

Yeah. Every step of the way, I just kept telling myself, my body knows how to do this. And I can, I can still do it, even though there's all these, you know, roadblocks being thrown my way.

That's awesome.

When they do it, what was interesting is just based on hospital, protocol, el and where I was in my pregnancy, they, they didn't want me to push in the operating room, just because of all the risks for the baby. So getting to 10 centimeters, and then going to push in. I'm so thankful to Jessica and her team to help help directly indirectly advocate for me not to do that. Oh, wow.

They said no, right. Do that. Yeah, you kept her where she was.

It was about to happen. And I don't know if I consciously did it, or my body was doing it anyways. But the baby happened to come out as we were playing. I also think that the the birth itself is so psychological and emotional. And so having the trust, and in a relationship that has been not only made during this high risk pregnancy, but then in previous pregnancies, I think that just all just works in your favor, to be able to have that response of the body that you're hoping for.

My son did need to have, he was there in the NICU. And there are all these other things that come into play as to after birth with a baby who has been affected by a sensitized pregnancy. You know, his bilirubin was an issue. Again, anemia, he actually went on to have three blood transfusions after birth. So, four to six months after birth, you're still managing the effects of these antibodies that were developed during pregnancy. And that, you know, doesn't end at delivery it as Jessica was alluding to it, it does continue on after and then now he's, he's great. He's making his own blood and he's doing wonderfully, you'd never even know this happen. So there is an endpoint, but it's it's a journey to get there.

I just am really, so supportive of Courtney for advocating for herself in this process, because despite we have this biological drive to birth our children in the way that we are meant to birth and despite all of any complexity of high risk pregnancy that she was facing, she really knew that despite it all it, it can be viewed as a physiologic process apart from the prenatal management of all that was going on. So I am just so grateful to her for getting the message out that it is possible to continue that relationship with like Trisha had mentioned, like the relationship with your midwife in it In certain practices or certain practices that don't do this so it was a gift that we were able to have the lowest intervention birth possible for her promote vaginal birth by having her be an adult, you know all sorts of different positions and have the lights low and her family present and we go I actually was out there for the birth itself, but from what I hear, it was pretty magical as it should have been. So I just congratulate you in not only supporting and advocating for that for yourself, but then getting this message out to other childbearing folks as well.

My heart is just so full, I mean, I could sit here and get really emotional about it because you know, like the weight of all the decisions that were made and but I never, you know, in my gut I knew I never had to question my care team and I wouldn't have been able to make the decisions that I made without their support. So like I feel Jessica said I also feel it was a gift and I'm just you know, it couldn't have been a better outcome despite the circumstances really.

Thank you for joining us at the Down To Birth Show. You can reach us @downtobirthshow on Instagram or email us at Contact@DownToBirthShow.com. All of Cynthia’s classes and Trisha’s breastfeeding services are offered live online, serving women and couples everywhere. Please remember this information is made available to you for educational and informational purposes only. It is in no way a substitute for medical advice. For our full disclaimer visit downtobirthshow.com/disclaimer. Thanks for tuning in, and as always, hear everyone and listen to yourself.

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About Cynthia Overgard

Cynthia is a published writer, advocate, childbirth educator and postpartum support specialist in prenatal/postpartum healthcare and has served thousands of clients since 2007. 

About Trisha Ludwig

Trisha is a Yale-educated Certified Nurse Midwife and International Board Certified Lactation Counselor. She has worked in women's health for more than 15 years.

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