Are there any statistics on the success of pregnancies if a mother HAS been alloimmunized to develop Anti-D?

Can pregnancies be successful as long as there is not fetomaternal hemorrhage?  What's the likelihood of a mother avoiding fetomaternal hemorrhage in future pregnancies?

  Just for knowledge, my mother-in-law had 6 Rh positive kids and she was Rh- Negative. There was no RhoGam back then. She came in later to have surgery and still had no Anti-D. She was not weak D positive either.

4 hours ago, Kathyang said:

  Just for knowledge, my mother-in-law had 6 Rh positive kids and she was Rh- Negative. There was no RhoGam back then. She came in later to have surgery and still had no Anti-D. She was not weak D positive either.

There are three types of people.  About 10 - 15% are non-responders, and never produce an antibody, however many times their immune system is challenged.  About another 70 - 80% are normal responders and, given sufficient stimulus, will produce antibodies.  The other 10 - 15% are super responders, and produce antibodies with the slightest insult to their immune system.  I once heard the wonderful Dr Ed Synder describe these people as being able to produce an anti-D after being given a "virtual transfusion".  When questioned as to what was a "virtual transfusion", he said that you showed a photograph of a D Positive red cell to such a person, and they produce an anti-D!!!!

I would suggest, Kathyang, that your mother was an extreme member of the first group.

Edited March 7, 20196 yr by Malcolm Needs
Figures slightly inaccurate.

4 minutes ago, Malcolm Needs said:

There are three types of people.  About 20% are non-responders, and never produce an antibody, however many times their immune system is challenged.  About another 60% are normal responders and, given sufficient stimulus, will produce antibodies.  The other 20% are super responders, and produce antibodies with the slightest insult to their immune system. 

I would classify my wife in the super responders category.

To attempt to answer the first question, it depends on a number of variables.  To start with, assuming she has the same father for all her children, what is his genotype?  R1R2 or R1r.  It makes a difference.  

On another note, FMH during the pregnancy will only be a factor if the baby is D positive and mom's titer needs a boost.  If mom starts with a high enough titer FMH during the pregnancy is not required for sever HDN.  My daughter was born with sever HDN and there was no known FMH during the pregnancy and all of the antibody studies suggested that she should not have been as affected as she was.  

Bottom line, there is no cut and dried answer to your question and honestly, there never is in the wonderful world of blood banking.  I suggest you get used to gray because black and white rarely if ever exists.  

My aunt had 3 children in the 60's. First baby was OK, second one was jaundiced and my third cousin had to have an exchange transfusion!

4 hours ago, studenttttttt said:

Are there any statistics on the success of pregnancies if a mother HAS been alloimmunized to develop Anti-D?

Can pregnancies be successful as long as there is not fetomaternal hemorrhage?  What's the likelihood of a mother avoiding fetomaternal hemorrhage in future pregnancies?

I am unaware of any such statistics being published studenttttttt, but I will tell you of some other statistics, and of some of my own experiences.

Prof. Patrick Mollison and his coworkers found that most people require at least 5mL of D Positive blood to stimulate the primary response to produce an anti-D (although the so-called super responders will do so with as little as 1mL), however, a secondary response will often occur with as little as 0.3mL of D Positive blood, even in a normal responder and, as John C. Staley states in his post (which came through as I was typing this) it also depends upon the Rh haplotype of the father (the R¹ haplotype has far fewer D antigen sites per red cell than the R² haplotype).,  It also depends on whether the FMH is acute or chronic, chronic being worse in this case.

From my own experience, I was on the Council of the British Blood Transfusion Society, when the National Institute of Health and Care Excellence (NICE - sometimes facetiously known as the National Institute for Curbing Expenditure), was performing a cost - benefit analysis on giving routine antenatal anti-D prophylaxis (RAADP) (and, as can be deduced from the facetious name for NICE, that they took some convincing), but sufficient numbers of cases were shown for them to agree to RAADP, which showed that very few pregnancies went to term without some form of "silent" foeto-maternal haemorrhage.  This means that the likelihood of avoiding another FMH in future pregnancies is remote.

All that having been said, and although the production of allo-anti-D cannot be "switched off" (although it can be "reduced" by the judicious (and very expensive) use of IVIgG during the pregnancy, we use to follow ALL such pregnancies in our area (some 53 hospitals) and not all resulted in a dangerous rise in antibody levels, so further pregnancies can be "naturally" successful, but these days, with the seemingly miraculous work of Foetal Medicine Units, even pregnancies involving really high titres of anti-D can be "salvaged" (a horrible term, but that is the word used).

Thanks! Let's say there is a slight FMH. Does that FMH eventually heal, preventing the mom's Anti-D from further contact with fetal RBCs?

Is that why so many fetuses survive HDFN even if there is Rh incompatibility?

10 hours ago, studenttttttt said:

Thanks! Let's say there is a slight FMH. Does that FMH eventually heal, preventing the mom's Anti-D from further contact with fetal RBCs?

Is that why so many fetuses survive HDFN even if there is Rh incompatibility?

The actual place where there is a feto-maternal haemorrhage probably will heal (although some of these are chronic), but by then the damage has been done.  If the mother is going to make an allo-anti-D, she will have been stimulated so to do.  However, it is not through the "fistula" between the foetus's and the mother's circulation that the anti-D gets to the foetal circulation, but by passing through the placenta.  Indeed, not only does the maternal IgG pass through the placenta, but it is actively transported across the placenta, so that the concentration of the anti-D is often higher in the circulation of the foetus, than it is in the circulation of the mother.  The reason so many foetuses survive HDFN even if there is Rh incompatibility is mostly down to the skill and dedication of the staff who work in Foetal Medicine Units, all of whom deserve utter admiration.

It should be noted that IgG crossing the placenta is, over all, a good thing in that this is the mechanism by which the mother is able to confer active immunity to many diseases to the fetus which lasts for some time after birth.  

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The reason so many foetuses survive HDFN even if there is Rh incompatibility is mostly down to the skill and dedication of the staff who work in Foetal Medicine Units, all of whom deserve utter admiration.

Thanks for your answer. In the cases of alloimmunized women who lack/forgo prenatal care for their 2nd or future pregnancies, how is it that a O-Pos fetus could survive to near term or term even with critical titers?

I understand they're severely jaundiced by this point, but why do some survive and have moderate/severe jaundice and others don't (miscarriage, hydrops, stillbirth)?

9 hours ago, studenttttttt said:

Thanks for your answer. In the cases of alloimmunized women who lack/forgo prenatal care for their 2nd or future pregnancies, how is it that a O-Pos fetus could survive to near term or term even with critical titers?

I understand they're severely jaundiced by this point, but why do some survive and have moderate/severe jaundice and others don't (miscarriage, hydrops, stillbirth)?

I think the only people who can answer this adequately would be immunologists and those who work in Foetal Medicine Units, but I would guess, and it really is a guess, that it could have something to do with the molecules that actively transfer the maternal antibody across the placenta are swamped, and the D antigens on the foetal red cells are blocked by massive amounts of maternal anti-D.