Anti-D in pregnancy: how we haven’t moved on…

AN anti-D quoteThe first Cochrane review of the research relating to the administration of anti-D during pregnancy was undertaken in 1996.

Nearly twenty years later, September 2015 saw the publication of the latest update. During that time, however, the only changes have been to the format, as the Cochrane Collaboration has updated their approach to the presentation of information. No relevant new trials have been published, and the reviewers’ conclusions haven’t really changed.  In fact, here are the results of that first review, which was published in the online Cochrane database in 1999:


“Two average to poor-quality trials, involving over 4500 women, compared anti-D prophylaxis with no treatment. When women received anti-D at 28 and 34 weeks’ gestation, relative risk (RR) of immunisation during pregnancy was 0.42 (95% confidence interval (CI) 0.15 to 1.17); after the birth of a Rh-positive infant the RR was 0.42 (95% CI 0.15 to 1.17); and within 12 months after birth of a Rh-positive infant the RR was 0.41 (95% CI 0.16 to 1.04). While none of these differences were statistically significant, the risk difference (RD) between anti-D and no treatment was significant (RD -0.01, 95% CI -0.01 to 0.00) suggesting reduced incidence of immunisation after anti-D prophylaxis.

In the higher dose trial (100 µg; 500 international units (IU) anti-D), there was a nonsignificant reduction in immunisation at two to 12 months following birth of a Rh-positive infant in women who had received anti-D (RR 0.14, 95% CI 0.02 to 1.15). However, women receiving anti-D were significantly less likely to register a positive Kleihauer test (which detects fetal cells in maternal blood) in pregnancy (RR 0.60, 95% CI 0.41 to 0.88) and at the birth of a Rh-positive infant (RR 0.60, 95% CI 0.46 to 0.79). No data were available for the risk of Rhesus D alloimmunisation in a subsequent pregnancy. No differences were seen for neonatal jaundice.” (Crowther and Middleton 1999)


In other words, although the trials seem to show some benefit to antenatal anti-D, this is not equivocal, the studies are of average to poor quality and some significant questions and wider issues remain unanswered and undiscussed. So you might think that we would either

(a) do more and better designed scientific research trials to get some better evidence, and/or

(b) delay offering anti-D in practice until we have some better evidence, especially given that

.       (1) anti-D is a blood product (which makes it even more worthy of our respect and care than usual, because blood products can carry viruses, lead to serious allergic reactions and cause other notable problems);

.       (2) very few rhesus negative pregnant women would be affected, as the risk is very low, and a particularly tricky element of this area is that a proportion of rhesus negative women will be carrying a rhesus negative baby and so will not be at any risk of isoimmunisation;

.       (3) there is evidence that a good part of the problem could be solved another way, if anti-D was offered at appropriate times and in response to potentially sensitising events; and

.       (4) we haven’t carried out much work looking into the potential risks and side effects of anti-D to the mother and her current baby, neither of whom directly benefit from its administration or, indeed, explored the wider issues and ramifications of this more fully.


In practice, and despite these factors, most Western systems of maternity care have at some point in the past couple of decades adopted the practice of offering (and, as ever, I use this term loosly but insistently, because we have to model what we want to see even if it isn’t the current reality) antenatal anti-D to the rhesus negative pregnant women who are accessing mainstream maternity services. Not all of these women want it, of course, but many do. I have lectured widely on this topic and this has led me to understand that in some areas, including much of the UK, many of the people offering antenatal anti-D to women would love to be able to explain the ins and outs of this issue but don’t feel able to do so, generally because they don’t have the time and/or the confidence to go against the party line.


And yet, as the authors’ conclusions from the latest review shows, we still don’t have good evidence that this intervention is effective or helpful and many concerns and questions remain.

Existing studies do not provide conclusive evidence that the use of anti-D during pregnancy benefits either mother or baby in terms of incidence of Rhesus D alloimmunisation during the pregnancy or postpartum, or the incidence of neonatal morbidity (jaundice) (low to very low quality evidence). However women receiving anti-D may be less likely to register a positive Kleihauer test in pregnancy and at the birth of a Rh-positive infant (low quality evidence). Fewer women who receive anti-D during pregnancy may have Rhesus D antibodies in a subsequent pregnancy, with benefits for the baby, however this needs to be tested in studies of robust design.


Antenatal anti-D is one of those pregnancy and birth interventions often offered without full information but within a context painted in shades of fear and risk. This is really unhelpful for pregnant women and their families. If you’d like to explore this topic further, I have written a series of posts and articles, which you can access from the following links:

Does antenatal anti-D help the current baby?

How to save 40,000 women a year from having an unecessary blood product

Anti-D choices remain limited

Yet more evidence to help women avoid unnecessary anti-D

and a whole series on anti-D (focused mainly around postnatal administration) which starts here.

Finally, here’s the link to the latest version of the Cochrane review if you’d like to read it in full.


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Crowther CA, Middleton P. Anti-D administration in pregnancy for preventing Rhesus alloimmunisation. Cochrane Database of Systematic Reviews, Issue 2. DOI: 10.1002/14651858.CD000020
McBain RD, Crowther CA, Middleton P (2015).  .  Article first published online: 3 Sep 2015. DOI: 10.1002/14651858.CD000020.pub3

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