The Rh factor and hemolytic disease of the newborn

This is how I’m going to structure things (at least until I figure out a better way or someone asks a question): I have gotten my hands on a variety of old GRE subject tests, and I have gone through them and read the questions. During my study groups, I have the students take practice tests and we go over the answers. I’m going to post one (or two or three) question(s) that are about a particular subject, then explain the concepts that are involved. How’s that? Good! Let’s get started.

Question: A homozygous, Rh-positive man (RR) marries an Rh-negative (rr) woman. Their first child is normal, but their second child has hemolytic disease (Rh disease). The first child did not have hemolytic disease because….

Alright–this questions is mostly about the Rh factor and its effect on the unborn child. First: the vocab of this question.

Homozygous–the condition of having two identical alleles for a particular gene
Rh-factor–a specific antigen present on the surface of the red blood cell
Hemolytic disease–a condition in which the red blood cells of an Rh-positive fetus or newborn are destroyed by anti-Rh antibodies previously produced in the bloodstream of an Rh-negative mother.

The first thing you need to do when reading a question about biology is to dissect the question itself. This questions has a lot of vocab and parenthesis that may cause confusion. Read the question at least twice to get at the real meat. The question introduces you to a couple with, now, two children. We learn the genotype (genetic makeup) of the parents: both are homozygous for the Rh-factor; dad is homozygous dominant for the Rh-factor, while mom is homozygous recessive.

The question is really testing your knowledge of red blood cells and the antigens present on the cells. An antigen is anything that causes an immune response. Every person has a blood type depending up on the glycoproteins (carbohydrates attached to proteins) attached to the red blood cell membrane. The lucky person who discovered these glycoproteins decided to give each type a letter: A or B. A person who has glycoprotein “A” on his blood cells has type A blood. A person who has glycoprotein “B” has type B blood. A person who has both glycoproteins on his blood cells has type AB blood, and a person with neither of these glycoproteins has type O blood.

What these blood types are missing is that “+” or “-” that you all see on your birth certificate. The positive or negative is called the Rh-factor, and either you have it or you don’t. “Rh” stands for rhesus, and was named for the rhesus monkey, which is where the protein was first noticed. This protein reacts just like the other glycoproteins on your blood cells–if your body recognizes the antigen (glycoprotein) then it will not attack it. If your body doesn’t recognize the antigen, then it will initiate the non specific and specific defenses to attack the perceived threat. If this was the first time your body saw the antigen, the non specific defenses would take care of the problem, while the specific defenses created antibodies to protect the body from future invasions. (Well, actually it’s a bit more complicated than that, but I’ll go into the intricacies of immuno-defense in a later post).

Your blood type becomes important when you need blood from a donor, or you are donating blood to someone who needs it. In the case of an emergency, hospitals use type 0- blood, since these red blood cells have no antigens on them at all, any person will accept this blood into his veins without triggering the immune system. This same idea applies to the transfer of blood from mother to child.

During most of pregnancy, the fetal circulatory system is closed off from the mother’s circulatory system. The fetus produces its own red blood cells, which accept oxygen and nutrients from the mother’s blood stream via capillaries in the placenta. The mother’s red blood cells do not cross over to the fetus, and the fetus’s red blood cells do not cross into the mother’s blood stream. During the trauma of birth, however, blood exchange happens. This usually isn’t that big of a deal, however. Even if the baby’s blood type is different from the mom’s, mom’s immune system will take care of any foreign blood cells quickly (and produce antibodies against future invasion from these blood cells). A problem arises only during the second pregnancy and in relation to the Rh-factor.

If mom is Rh-positive, it doesn’t matter what her child is (Rh-negative or Rh-positive) her body will not react to the child’s blood during birth. Her immune system will recognize the Rh protein, and therefore not attack a cell that is Rh positive. If it encounters a cell without the Rh-factor, it won’t recognize the cell as foreign because it is the protein present on the cell’s membrane that identifies it as foreign. If there’s no protein, there’s no problem. However, if mom is Rh-negative, her body will recognize any Rh-positive blood cell as foreign, and activate her immune system accordingly. The Rh-factor is passed on via normal Mendelian genetics, with Rh-positive being dominant and Rh-negative being recessive. Therefore, it is possible to determine the possible genotypes of the child in regards to the Rh-factor using a simple Punnett square.

R R
__________________

r Rr Rr

__________________

r Rr Rr

__________________

If mom is Rh-negative, as she is in this GRE question, then her first pregnancy will proceed normally. No matter what the blood type of her baby, her blood won’t come in contact with the baby’s blood cells (and therefore any possible antigens) until birth. After birth, the baby is pretty much safe from any antibodies mom’s immune system produces. The problem arises when mom and dad want to give junior a little brother or sister. If mom is Rh-negative and bundle-of-joy #1 is Rh-positive, mom’s immune system gets exposed to the Rh antigen. Her immune system reacts accordingly, destroying the perceived threat, and producing antibodies to protect her against future invasions. If bundle-of-joy #2 is also Rh-positive, mom is already primed and ready to kill off any Rh proteins she sees. Red blood cells don’t cross over the placental barrier, but antibodies do. Can you see the problem? Mom’s antibodies attack the fetus’s red blood cells, causing the fetus to die from lack of oxygen and nutrients, or causing the baby to be born severely anemic. This condition is called “hemolytic disease of the newborn.” Look familiar? Yep! This is the disease to which the question is referring.

So, now that we know the basics, let’s get back to the question:

A homozygous Rh-positive man marries an Rh-negative woman. Their first child is normal, but their second child has hemolytic disease.

This part makes sense, doesn’t it? We know the genotype of both mom and dad, so we can use a Punnett square to predict all the possible genotypes of the children: Rr, Rr, Rr, and Rr.

It appears that all the children will be heterozygous for Rh-positive. Now, we know that there may be a problem between an Rh-negative mother and an Rh-positive fetus due to mom’s immune system. However, mom’s immune system is not exposed to the Rh antigen until the moment of the first baby’s birth, so baby #1 is protected. When mom gets pregnant again, though, the child is afflicted by hemolytic disease. “Hemo” refers to blood, while “lytic” refers to bursting; “hemolytic” is the bursting of red blood cells. Bad! This occurs because mom’s immune system is primed and ready to kill off the Rh-antigen the moment it sees it, so baby #2 is attacked as soon as he begins to make red blood cells.

Good! So there is the main concept behind the question. Let’s get to the actual question part, though:

The first child did not have hemolytic disease because….

Well, can you answer the question? Yep, the first child didn’t have hemolytic disease because mom’s immune system had not yet been exposed to the Rh-antigen and therefore did not have any antibodies capable of crossing the placental barrier and attacking the fetus’s red blood cells.

Here are the multiple choice answers given to this question:

A) the child was heterozygous (Rr)
B) the child lacked the Rh antigens
C) the mother had a previous blood transfusion that protected the child against antibodies
D) anti-Rh antibodies present in the mother were destroyed by the child’s immune system
E) anti-Rh antibodies were not induced in the mother until the delivery of the child

So, given what we know, the answer to this question is E. Yes, the child was heterozygous (Rr), but this does not answer the question, and is not the reason the child did not have hemolytic disease. Because the child was Rr, we know he had the Rh antigens (remember Rh-positive is the dominant trait), so answer B doesn’t even make sense. Answer “C” just seems ridiculous to me, and hopefully to you, too. Blood transfusions don’t change the mom’s immune system, nor what diseases she is protected against. A blood transfusion is primarily used to ensure the presence of adequate red blood cells and blood volume in the circulatory system. It has nothing to do with protecting a fetus against antibodies. The growing fetus is still building its immune system, so he must rely on mom for protection and immunity. He doesn’t yet have the capacity to fight off foreign cells, so he has no defense against mom’s antibodies. Therefore, option “E” is the correct answer!

How is it, then, that Rh-negative moms have more than one child? Why aren’t they all still born? Scientists attacked the problem of hemolytic disease some time ago. One of the first questions a doctor asks a pregnant couple is their blood types. If mom is Rh-negative and dad is Rh-positive, then during the birth (or soon thereafter) mom will be injected with a serum named RhoGAM, which contains antibodies against the Rh antigen. This serum takes care of any Rh-positive red blood cells circulating in mom’s blood, so her immune system doesn’t have the chance to get all annoyed. She doesn’t make any of her own antibodies against the Rh antigen, and her future children are protected.

Questions? Comments? I hope this helped!

20 thoughts on “The Rh factor and hemolytic disease of the newborn”

  1. Yay, it was great hearing that all again. Even if I didn’t already know it I would have totally understood it this time around. I love blood types, it was one of my favorite topics in A&P. I really should just sit in your classroom one of these days:P Welp, my nerdy self will be looking forward to the next question:D

  2. I find this site very helpful… i am looking forward to more input.

    Thanks!!

  3. Can you please inform what happens if they give birth to a 3rd child without the Rhogam? Will it still be the same case as the 2nd child?

  4. Re: “Can you please inform what happens if they give birth to a 3rd child without the Rhogam? Will it still be the same case as the 2nd child?”

    Yes, it’s the same for the third as for the second–once you have been exposed to the antigen, then you will know it forever. You can have the treatment as many times as you have children, however, which is why doctors ask if this is the last baby or not. Did that answer your question? Thanks!

  5. I was born in 1954 and was the third child and the last. Mom lost her third which really makes me the forth by RH standards. I have put together a blog and over time hope to update it with more information. I am looking for as much information as I can on RH disease survivors. I my blog, which someday I hope to have a WWW, I get into a little bit about my experiences and the problems I have been having since birth. Other than those (RH survivors) I have meet over the years there is very little I can find out about RH disease survivors. There does seem to be some similarities with RH survivors, depression, anxieties and so on. Whether this is from the RH disease or the exchange transfusions or maybe just that we are born FU with out any excuse, who knows or what ever; I seem to be on this path to seek out and find as much on RH disease survivors as possible. If you can help please go to my blog, I am looking for input.
    Doug Allan

  6. I was born in 1954 and was the third child and the last. Mom lost her third which really makes me the forth by RH standards. I have put together a blog and over time hope to update it with more information. I am looking for as much information as I can on RH disease survivors. I my blog, which someday I hope to have a WWW, I get into a little bit about my experiences and the problems I have been having since birth. Other than those (RH survivors) I have meet over the years there is very little I can find out about RH disease survivors. There does seem to be some similarities with RH survivors, depression, anxieties and so on. Whether this is from the RH disease or the exchange transfusions or maybe just that we are born FU with out any excuse, who knows or what ever; I seem to be on this path to seek out and find as much on RH disease survivors as possible. If you can help please go to my blog, I am looking for input.
    Doug Allan

  7. Hi Adrienne: Thanks for posting my comments.

    I have a question and excuse me; this is fairly new to me so I am trying to building an understanding of all this.
    If a baby born to a RH negative mother and a RH positive father is RH positive then the mother’s immune system is going to go into Rambo mode and get ready for the next baby; right!
    If the next baby is RH negative there is no cause for concern but if the next baby is RH positive the immune system of the mother starts its god give right to defend its turf and kill the red blood cells of the next infant, right?
    So a RH – mother and RH + father can have a healthy baby only if the baby is RH negative and so on for the next babies, right?

    Next: The problem of damage to the infant starts before birth when the baby starts to manufacture its own red blood cells and if so can you tell me at what month of pregnancy does this start? I was under the impression the damage to the red blood cells didn’t start until birth.

    Thanks Doug

  8. Hey there Doug! In answer to your questions:

    1. “If a baby born to a RH negative mother and a RH positive father is RH positive then the mother’s immune system is going to go into Rambo mode and get ready for the next baby.” Correct! You’re on the right track there.

    “If the next baby is RH negative there is no cause for concern but if the next baby is RH positive the immune system of the mother starts its god give right to defend its turf and kill the red blood cells of the next infant, right?
    So a RH – mother and RH + father can have a healthy baby only if the baby is RH negative and so on for the next babies, right?”

    Yep, that’s the gist of things. However, doctors can interfere with the mother’s immune system BEFORE she even produces the antibodies destined to kill the next RH+ baby. Remember, she won’t make them until she sees them, which only happens when baby’s blood crosses into her’s during the first RH+ birth. If the doctors know the first baby is RH+ and the mother is RH-, then they will prevent mom from producing antibodies. The result is a safe baby the next time around, even if it is RH+. If the doctors don’t do anything, however, then you are correct in thinking the next RH+ baby is going to have some problems.

    2. “The problem of damage to the infant starts before birth when the baby starts to manufacture its own red blood cells and if so can you tell me at what month of pregnancy does this start? I was under the impression the damage to the red blood cells didn’t start until birth.”

    A fetus starts producing red blood cells well before birth–around the 4th or 5th week after fertilization. The heart starts beating at week 5, and it needs something to move! Now, antibodies, unlike blood, can cross the placenta from mom to baby. So if mom has antibodies in place against RH+ blood, they will get into the baby from the moment mom starts feeding him or her in the womb. As soon as red blood cells exist, they will be attacked. So the problem happens very early in the second RH+ child, and can result in a miscarriage.

    I hope this helped!

  9. Thanks Adrienne: It was a big help. I am still searching for information on Rh disease survivors but there is not much on the www but I am learning a lot about the disease and how it affects the baby. It seems the bile build up in the body crosses the blood brain barrier and this is how the brain damage occurs. One other question I am having a hard time understanding.
    Is the baby given RH positive of RH negative blood for the exchange transfusions? I thought it would be RH + blood, since the baby is RH +, but I read an article saying it is RH- blood used in the blood exchange transfusion? It does make since to use RH – blood since the damage is being done to the RH + red blood cells.
    Thanks

  10. what is rh blood disease? One of the posters commented on that; #RH Survivors. What happens if the mother didn’t have the treatment, and then a child is born. A survivor. Do they have disabilities?

  11. i have a friend who is rh negative and the father is her husband is also rh negative she just went threw her 3rd miscarriage. they have no children tho they are trying. she is healthy and does not smoke. could this rh negative be an issue. all i know is that they had to give her that shot after she lost the last one. please if you could make me understand this any better it would be a great help, because my friend thinks her body is killing her babies…thankyou

    traci

  12. Hey there Taci! I’m not sure what is going on with your friends–since they are both RH negative, there should be no problem with the RH factor and the pregnancy. There are many, many reasons for a woman to miscarry, however, so it may be that one of these reasons is affecting your friends. I don’t thing the RH factor has any influence. I hope this helps!

    –Adrienne

  13. My wife was typed as O neg, when she delivered our first child in Dec of 1978. I am O pos. She was given a large amount of RhoGam, as was the case when she had our other two children, the last being in Dec of 1984. We both donate blood to the Red Cross, and they insist that my wife is O pos. Is this possible, or was a mistake made back in 1978? If so, are there any consequences to the RhoGam given her?

  14. thanks so much! i just did a practice GRE, and that question was on it- now i know how to answer it!

  15. It is rather interesting for me to read the article. Thank author for it. I like such themes and anything that is connected to them. I would like to read a bit more on that blog soon.

  16. Rather interesting place you've got here. Thanks for it. I like such topics and anything connected to them. BTW, why don't you change design :).

  17. Hi Adrienne,
    I posted a comment a while back, RH survivors. As I said earlier I am an Rh survivor. I have recently been diagnosed with Borderline Personality Disorder and am on this quest to better understand the why's as to my personality disorder. From what I have learnt when a baby is exposed to a traumatic event it can affect them in a number of different ways, including emotionally later on in life. I suspect the traumatic experience of the exchange transfusions has had a negative effect on me and I am looking for as much information, books, web sites, articles or whatever I can find about the exchange transfusions and the effects they have on people. I have been in contact with some other survivors and they seem to be having the same problems I am having. If you or anybody else can help in any way I would greatly appreciate it.
    Thanks
    Doug Allan

  18. As a Rh surviver, having had an exchange transfusion at birth replacing my Type O:Rh-pos with Type O: Rh-neg, should my body have since produced Rh neg or positive? What determines the type RBCs reproduced, the DNA (in which case it would be Rh-pos), or the new RBCs from the transfusion (in which case I would now be RH-neg). If my body produced new RBCs that were Rh-Pos, wouldn’t my mother’s antigen that I inherited from her continue to attack the newly produced Rh-pos RBCs? I have always thought I was O-Pos but now I am confused. When I received blood following surgery (after my BP dropped) they gave me O-Pos blood and I immediaely suffered an A Fib attack. Was I rejecting the O-Pos blood?

  19. Hello Adrienne, Searching online today looking for survivors of being born with RH Disease back in 1960, and not finding very much information. Thank you for what you’ve written here. I was born in 1960 with the RH Disease, and wondering how that has effected my health through today. I’ve had continual issues with malabsorption and 6 years ago I was diagnosed with a muscle disease. Do you know of any information for those of us born with this and what the long term health effects are? PS. I notice you were at Texas A&M University. I’m your neighbor, about 50 miles to the East in Centerville. After reading about a link between RH Disease and Biotinidase Deficiency, I’m wondering if taking a high level of Biotin could help correct underlying genetic problems today?

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