Rh-mediated hemolytic disease of the newborn

Here is an interesting boards-type question about Rh-mediated hemolytic disease of the newborn and Rhogam administration:

A 22-year-old woman, gravida 1, para 0, who is Rh-negative, delivers a full-term Rh-positive neonate. The mother is given prophylactic anti-Rh (D) immune globulin (Rhogam) immediately post partum. During her second pregnancy three years later, she is screened each trimester for anti-Rh antibodies. An indirect antiglobulin test done during the third trimester indicates the presence of anti-Rh antibodies in her serum. Which of the following is the most likely mechanism for the occurence of these maternal antibodies?

A. Anamnestic production of maternal anti-Rh antibodies
B. Intrauterine transplacental fetal-maternal hemorrhages during the second pregnancy
C. Residual circulating prophylactic anti-Rh immunoglobulin
D. Transplacental passage of fetal IgG anti-Rh antibodies

———————————————————————

So the question is about the classic situation in which Rh-mediated HDN occurs: an Rh negative mom gives birth to an Rh positive child, and then has another pregnancy in which the fetus is Rh positive. Without Rhogam, this situation can be deadly for the fetus, because the mom will make anti-Rh antibodies at the time of delivery of the first baby, and those antibodies stay around and attack any subsequent Rh positive fetus (anti-Rh antibodies are IgG in nature, so they cross the placenta easily).

The situation in this question is a little different, because the mom received Rhogam (anti-Rh antibody) after the first pregnancy. Rhogam binds to any fetal cells that have been transferred into the mom, effectively “sopping up” any available antigen, so mom doesn’t get the chance to make her own anti-Rh. This should have prevented any production of anti-Rh by the mom at the time of delivery of the first baby. That’s good. However, with subsequent Rh-positive pregnancies, you need to continue giving the mom Rhogam so that she does not make anti-Rh antibodies to those fetuses! Rhogam doesn’t last long – the half-life is 23-26 days. So the Rhogam you give with the initial pregnancy will not last long enough to cover subsequent pregnancies; you need to give it again. And it’s best to give it twice: once during pregnancy (usually at 28 weeks) to sop up any potentially transferred fetal cells (which can sometimes happen during trauma, or with intra-placental testing or something like that), and once at delivery (which is when the biggest chance of feto-maternal hemorrhage is. There’s usually at least some transfer of fetal cells into mom at that point).

It doesn’t sound like this mom got Rhogam at 28 weeks during her second pregnancy, so any feto-maternal hemorrhage during the pregnancy would run the risk of inducing anti-Rh production in the mom. That is probably the cause of the anti-Rh antibody discovered in the third trimester: there was a feto-maternal bleed some time during the pregnancy, and mom made anti-Rh antibodies in response to the fetal cells (they don’t say explicitly that this fetus is Rh positive, but I think we can assume so. It’s the only way the question makes sense.).

To answer the question:
A. is wrong, because the anti-Rh antibody is not anamnestic (that is, against the first fetus) – because the mom was given Rhogam at the time of delivery of the first fetus.
B. is correct, for the reasons discussed above.
C. is wrong; Rhogam’s half life is short – it would be well out of the circulation by the time of the second pregnancy.
D. is wrong; the fetus would not make anti-Rh antibodies. For one thing, we’re assuming the fetus is Rh positive (in which case, he/she would not make anti-Rh antibodies!). For another thing, you need to be exposed to the Rh antigen in order to make anti-Rh (unlike the ABO system, in which you automatically make anti-A and anti-B without being exposed to those antigens), and there’s no way the fetus would have been exposed to the Rh antigen.

Note: the beautiful and delicate image of the fetus above was taken by lunar caustic and can be found at: http://www.flickr.com/photos/lunarcaustic/2128618333/.