Happy 2014! My first post this year is also the first in a new occasional series which will be tagged Questions&Answers … these are my responses to questions that I get asked frequently. As ever, they are not intended to be taken as advice, but as jumping off points for further exploration of issues and decisions.
Over the past few weeks, a number of people have asked me variations on the same question: does prophylatic anti D offer protection to the baby in a current pregnancy? My understanding is that it does not; that antenatal anti-D is ‘all about the next baby’, although in order to understand why this is the case, we need to start with a bit of immunology…
Firstly, let’s recall that an antigen is a substance that is foreign to the body. When an antigen is detected in the body, the cell plasma cells start to generate antibodies to counteract that antigen. This is called a primary immune response and it leads to the production of immunoglobulin M, or IgM antibodies. Once these IgM antibodies have counteracted the offending antigen, the body stops producing them, but the body retains the memory of how it needs to respond if the same antigen enters the bloodstream again. If the same antigen does enter the body again, the body mounts what is known as a secondary immune response. This occurs much faster than a primary immune response and, even more importantly for our purposes, the antibodies that it produces will be in a form called Immunoglobulin G or IgG.
The primary response that I have just described is exactly what can happen if a rhesus negative women encounters rhesus positive blood – and let’s assume for a moment that she doesn’t have access to synthetic anti-D, so in this paragraph we’ll just think about what her body would do naturally. Her body may mount a primary immune response and make IgM antibodies to the rhesus positive cells. Once they have all been cleared, antibody production will slow down and then stop, but we now have a problem. If she becomes pregnant with another rhesus positive baby in the future, her body now has a ‘template’ to make IgG antibodies against the baby’s blood and problems can ensue. This is why synthetic anti-D is given: it ‘mops up’ the offending antigens, preventing the need for the woman’s body to make natural anti-D antibodies which in turn means that future babies are not at risk from those antibodies.
A hugely important thing to know at this point is this: IgM antibodies are about six times as big as IgG ones. IgG antibodies can cross the placenta, IgM antibodies can’t. So a woman who is mounting a primary immune response to rhesus positive blood cells is not going to be producing the kind of antibody that can cross the placenta to harm her growing baby. But a woman who is mounting a secondary immune response will produce the far smaller IgG antibodies, and those can cross the placenta… During the primary immune response which involves the big IgM antibodies, the baby in utero is not at risk.
But the difference between the primary and secondary immune responses is only one part of the answer to this question. Another element of this is the timeframe of the process of antibody production. My understanding is that, while some antibodies can be produced within days, the primary immune response to the rhesus factor can take up to six months. So by the time you take into account the fact that the rhesus factor isn’t produced until near or during the second trimester of pregnancy, then you allow six months for the cessation of the primary immune response (which, don’t forget, does not pose a threat to the current baby because IgM is too big to cross the placenta), well there’s not much chance of that same baby encountering IgG through a secondary immune response because he or she has almost certainly been born. His future siblings may encounter problems if they are rhesus positive, because now their mother has a template for creating IgG antibodies that are small enough to cross the placenta into the baby’s bloodstream, but antenatal anti-D is not about protecting the current baby.
There is a lot we don’t know in this area. We know that pregnant women have altered immune systems. They have to in order that their bodies do not reject their babies, as of course half of the genetic material that makes their babies comes from outside of their body. We are beginning to form some theories about how the altered immunity of a pregnant woman might be related to some of the problems that pregnant women occasionally face. But there is so much we don’t know about maternal and fetal immunity in general and the issues surrounding the administration of anti-D in particular. For instance
- As I said above, we know that IgG can cross the placenta, which we might surmise is good when this means that babies in utero gain immunity to things that their mother has already gained immunity to, but not really ideal in relation to the creation of anti-D. Given that nature generally gets it right most of the time, is there more that we don’t yet understand about this?
- Because IgG can cross the placenta, when a woman decides to have synthetic anti-D during pregnancy in order to possibly protect her future babies, her current baby will get about 10% of the anti-D going into its bloodstream, but we don’t know what effect/s this might have on that baby. (Bear in mind that it might have different effects on rhesus positive and rhesus negative babies…)
But there are always more questions, and for now I hope that this has answered the question at hand and at least explained why synthetic anti-D given routinely in pregnancy does not benefit the current baby. It may indeed benefit future ones and please understand that, although this might seem detailed, it is only one tiny element of a bigger picture. Please also let me finish with a caveat: I am not an immunologist, and I am aware that our understanding of this area is developing apace. If anyone with more knowledge of this than I thinks they can improve this explanation, or feels any of it needs correcting, please use the contact form and let me know 😀
For lots more information on anti-D and related decision-making, see my book 🙂Anti-D in Midwifery: Panacea or Paradox?